SUZHOU, Chinaand SHANGHAI, Dec. 9, 2019 /PRNewswire/ -- Gracell Biotechnologies Co., Ltd ("Gracell"), a clinical-stage immune cell therapy company, today announced the progressive clinical outcomes for leading product candidates FasTCAR-19, Dual CAR-19-22, and Dual CAR-BCMA-19 at the American Society of Hematology (ASH) Annual Meeting in Orlando, Florida, held from December 7-10. Multiple pilot studies intend to evaluate the safety and efficacy of Gracell's first-in-class FasTCAR-19 (GC007F), Dual CAR-19-22 (GC012F) and Dual CAR-BCMA-19 (GC022F) cell therapy.

FasTCAR-19FasTCAR-19 or GC007F uses Gracell's patented FasTCARTM solution, which genetically modifies a patient's T-cells to express CD19-specific chimeric antigen receptor (CAR) for the treatment of B-cell acute lymphoblastic leukemia (B-ALL).

Utilizing the unique bioprocessing, FasTCAR-19 cells can be produced overnight through viral transfection in use of Gracell's proprietary fully-closed manufacturing system (from apheresis to filling). These cells are considered far more potent and durable in comparison to current market alternatives. To date, all 37 patient samples have been successfully manufactured. The process has been proven efficient, stable and duplicable, with a median 36.8% (range 13.1%-70.3%) transfection success and a median copies of 0.95 (range 0.2-4.21).

As of November, this investigational study enrolled 37 adult and adolescent patients aged from 14 to 70 years, who suffered from r/r B-ALL and had failed to respond to multiple prior lines of therapy, from eight clinical centers. All patients received a single infusion of FasTCAR-19 at one of the three-dose level (low: 0.6*10^5/kg; mid: 1.0*10^5/kg, and high: 1.6*10^5/kg), followed by prior conditioning regimen of fludarabine-cyclophosphamide (FC).

The treatment efficacy was assessed in 35 patients over 28 days of follow-up, of which:

During the over six month-durable remission period, FasTCAR-19 demonstrated a good level of persistence in line with previous clinical trials. In terms of safety, all 37 patients tolerated the single infusion of FasTCAR-19 at different dose levels, with no dose-limiting toxicities observed. The most common safety concerns were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) where mild to moderate side effects were observed. Across 30 patients in the low to mid doses group, only 5 (16.7%) manageable Grade 3 CRS and 5 (16.7%) manageable Grade 3 ICANS were reported; while the remaining 23 (76.7%) had Grade 1-2 CRS. The low to mid doses group will likely be selected for extensive study in future clinical trials.

Beyond single-antigen CAR, Dual CAR-T cells can deliver promising clinical outcomesSingle-antigen CAR-T cells have demonstrated considerable efficacy; however, antigen loss and high relapse rate have been observed in a significant number of patients. To combat this, treatments containing two separate CARs and dual transduction (GC022 targeting CD19 and CD22, GC012 targeting BCMA and CD19) were developed. Following positive results from in vitro and in vivo studies, human clinical trials have commenced testing the safety and feasibility of Dual CAR-19-22 and Dual CAR-BCMA-19 to treat B-ALL and MM, respectively.

Dual CAR-19-22

Dual CAR-19-22 or GC022 has achieved a manufacturing success rate of 20/20, without any patient loss due to manufacturing failure. Enrolled patients aged from 4-45 years old who has B-ALL, received a single infusion of Dual CAR-19-22 at one of the three-dose levels (low: 0.5*10^6/kg; mid: 2.0*10^6/kg, and high: 3.0*10^6/kg), under conventional bioprocessing. The study demonstrated a very good safety profile and high efficacy at mid to high doses.

The treatment efficacy was assessed in 20 patients with a 28-day follow-up, of which:

Dual CAR-19-22 proved effective on patients who had previously been treated with CD19 CAR-T cells and/or received allogeneic hematopoietic stem cell transplantation (allo-HSCT) for r/r B-ALL but failed to benefit from prior treatments. Among these five patients, four (80%) patients achieved MRD-CR with a 28-day follow-up. Surpassing the 3-month durable remission period, fifteenpatients still retain ongoing response.

Furthermore, Dual CAR-19-22 demonstrated an excellent safety profile, with 6/20 (30%) patients indicating no CRS, 14/20 (70%) reporting Grade 1 CRS. No ICANS events were reported.

Dual CAR-BCMA-19Dual CAR-BCMA-19 or GC012 has been demonstrated effective in eliminating multiple myeloma (MM) tumor cells both in vitro and in vivo. The first-in-human study showed a good safety profile and effectiveness. Beyond, FasTCARTM has successfully been applied to Dual CAR-BCMA-19, expected to enhance proliferation, potency, and migration in the human body.

"We are delighted to see that patients with relapsed/refractory B-ALL continue to gain substantial clinical benefit from FasTCAR-19. Furthermore, Dual CAR-19-22 with conventional bioprocess can generate promising clinical data. This marks our confidence to utilize FasTCAR technology to both Dual CAR programs for various indications," said Dr. William Cao, CEO of Gracell. "The results from our latest clinical trials reveal the immense potential of FasTCAR technology, and we are eager to see Gracell's highly efficacious, yet affordable therapies benefit more patients in China and worldwide."

About B-ALLAcute lymphoblastic leukemia (ALL), although rare, is one of the most common forms of cancer in children between the ages of two and five and adults over the age of 501. In 2015, ALL affected around 837,000 people globally and resulted in 110,000 deaths worldwide2. It is also the most common cause of cancer and death from cancer among children. ALL is typically treated initially with chemotherapy aimed at bringing about remission. This is then followed by further chemotherapy carried out over several years.

About MMMultiple myeloma (MM) is a cancer that forms in a type of white blood cell known as a plasma cell. MM cells are abnormal plasma cells (a type of white blood cell) that build up in the bone marrow and form tumors in many bones of the body. Healthy plasma cells make antibodies to help the body fight infection and disease. As the number of MM cells increases, more antibodies are produced. This can cause the blood to thicken and keep the bone marrow from making enough healthy blood cells. MM cells can also damage and weaken the bone. In 2018, MM affected around 160,000 people globally and resulted in 106,000 deaths worldwide3. Different types of treatments are available for patients with plasma cell neoplasms. Chemotherapy and targeted therapy are typical treatments; while stem cell transplant, biologic therapy, and radiation therapy, even surgery are also adopted.

About GracellGracell Biotechnologies Co., Ltd. ("Gracell") is a clinical-stage biopharma company, committed to developing highly reliable and affordable cell gene therapies for cancer. Gracell is dedicated to resolving the remaining challenges in CAR-T, such as high production costs, lengthy manufacturing process, lack of off-the-shelf products, and inefficacy against solid tumors. Led by a group of world-class scientists, Gracell is advancing FasTCARTM, TruUCARTM (off-the-shelf CAR), Dual CAR and Enhanced CAR-T cell therapies for leukemia, lymphoma, myeloma, and solid tumors.

CONTACT:

1https://www.cancer.org/cancer/acute-lymphocytic-leukemia/about/key-statistics.html2https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055577/3https://gco.iarc.fr/today/fact-sheets-cancers

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Gracell Announces Progressive Outcomes from Multiple Human Clinical Trials to Investigate FasTCAR and Dual CAR Cell Platform Technologies - PRNewswire

Bone Marrow Stem Cells Comments Off on Gracell Announces Progressive Outcomes from Multiple Human Clinical Trials to Investigate FasTCAR and Dual CAR Cell Platform Technologies – PRNewswire | December 9th, 2019

Using immunotherapy with genetically modified T cells that express chimeric antigen receptors or CARs designed to target tumor-associated molecules, have impressive efficacy in the treatment hematological malignancies.

A CAR is a synthetic construct that, when expressed in T cells, mimics T cell receptor activation and redirects specificity and effector function toward a specified antigen.[1]

In the treatment of cancer, this process is accomplished by linking an extracellular ligand-binding domain specific for a tumor cell surface antigen to an intracellular signaling module that activates T cells upon antigen binding.[1]

The presented studies include results from emerging second-generation cellular immunotherapy products that strive to overcome the limitations of existing products such as resistance and reduce toxicity and simplify treatment.

Cellular immunotherapy uses genetic engineering to enhance the ability of the immune system the bodys defense system against infection and disease to kill malignant cells in the blood, the bone marrow, and other sites, in order to keep cancer from coming back.

CAR T-cell TherapyChimeric antigen receptor T-cell therapies, better known as CAR T-cell therapies, are developed by harvesting a patients own T-cells, the immune systems primary cancer-killing cells, engineering them to target proteins specific to the surface of cancer cells, and reintroducing these modified T-cells back into the patients immune system to kill the cancer cells.

First generationFirst-generation CAR T-cell therapies primarily target CD-19, a protein found on the surface of most normal and malignant B cells in B cell cancers such as lymphoma. These therapies have been shown to produce long-term remissions in about one-third of patients with B-cell lymphomas that have not responded to prior therapies.

We are now seeing efforts to enhance the effectiveness of CAR T-cell therapy by designing products capable of attacking multiple targets, expand the availability of cellular immunotherapy to other blood cancers such as multiple myeloma and replace the complex manufacturing process required for CAR T-cell therapy with a uniform off-the-shelf product, noted Gary Schiller, MD, UCLA Health, an academic medical center which includes a number of hospitals and an extensive primary care network in the Los Angeles, California, region.

One of the phase I studies evaluates an off-the-shelf cellular immunotherapy product that targets two proteins found on the surface of lymphoma cells, including its potential to revive previously administered CAR T-cells that have stopped working.

Another study presents preclinical results for one of the first cellular immunotherapies to be based on off-the-shelf natural killer (NK) cells and the first, according to its manufacturer, to be genetically engineered to contain three active anti-tumor components.

The other two studies, also phase I studies, assess novel CAR T-cell therapies for multiple myeloma that test different dual-target strategies.

One investigational agent is genetically engineered to contain two proteins that attach to BCMA, a protein found almost exclusively on the surface of plasma cells, the immune-system cells that become cancerous in multiple myeloma.

The other is designed to target both BCMA and CD-38, another protein found on the surface of plasma cells. In both studies, many patients achieved minimal residual disease (MRD) negativity, which means that using highly sensitive testing fewer than one myeloma cell per 100,000 cells was identified in the bone marrow. Previous studies have shown that patients who achieve this milestone have a lower risk of relapse after more than three years of follow-up.

Dual-targeted CAR T-cell therapiesThe three phase I studies also hint at the possibility that dual-targeted CAR T-cell therapies might result in fewer patients experiencing moderate to severe cytokine release syndrome (CRS), a known adverse effect caused by an immune response in the body to the activated T cells that are attacking the cancer. CRS causes flu-like symptoms such as fever, body aches, and fatigue, and in severe cases can be life-threatening. Treatment with the drug tocilizumab can reduce CRS symptoms.

Dual-Targeted Antibody Elicits Durable ResponsesPatients with B-cell Non-Hodgkin Lymphoma (NHL) that had returned after or failed to respond to a median of three prior therapies showed complete responses (CR) and durable remissions after being treated with an investigational drug called mosunetuzumab (RG7828; Genentech/Roche). [2]

This investigational agent is a humanized, T-cell bispecific antibody designed to engage T cells and redirect their cytotoxic activity against malignant B cells. The drug works by activating the patients own T-cells, stimulating them to attack and kill cancerous B cells to which they have been introduced by the novel antibody.

Mosunetuzumab simultaneously binds to CD3 epsilon (CD3), a component of the T-cell receptor (TCR) complex, and to CD20, a B-cell surface protein expressed in a majority of B-cell malignancies. This results in crosslinking of the TCR, inducing downstream signaling events that leads to B-cell killing.

Among patients whose lymphoma progressed after treatment with CAR T-cell therapy, 22% had complete remissions when treated with mosunetuzumab. This new drug targets two proteins, one on the surface of tumor cells and the other on the surface of the recipients Tcells.

Unlike CAR T-cell therapy, mosunetuzumab is an off-the-shelf immunotherapy product that can be given to patients without having to genetically modify their T cells, noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T-cell therapy, he added.

The researchers observed many remissions continue after patients stop receiving the drug.

I have stopped therapy in some patients after six months and they have remained in remission. Some patients have remained in remission without additional therapy for more than a year, Schuster said.

New treatment options are needed not only for patients in whom CAR T-cell therapy has failed, but also for those patients whose lymphomas are getting worse so quickly that they cannot wait for CAR T-cell manufacturing, which takes several weeks, Schuster explained.

The data presented during the annual meeting of the American Society of Hematology included 270 patients (median age 62, 172 men) enrolled in the phase I trial in seven countries (the United States, Australia, Canada, Germany, South Korea, Spain, and the United Kingdom). All participating patients had B-cell lymphomas that had come back or not responded to a median of three prior therapies. Two-thirds of patients (67%) had fast-growing lymphomas; 85 (31%) patients had more slow-growing forms of the disease. In 30 patients (11%), the cancer was resistant to or returned after an initial response to CAR T-cell therapy; in 77 patients (29%), the disease had progressed after a stem cell transplant.

All patients were treated with mosunetuzumab by intravenous infusion. They had an imaging test at either six weeks or three months after starting therapy to assess the initial response to treatment, and responses continued to be followed every three months thereafter.

Forty-six of 124 patients with fast-growing lymphomas (37%) had measurable decreases in the extent of their cancer (objective response); 24 of 124 patients (19%) saw all detectable tumors disappear (complete response). A higher response rate was observed in patients with higher exposure to mosunetuzumab. Among patients with slow-growing lymphomas, 42 of 67 (63%) had objective responses and 29 of 67 (43%) had complete responses. Both objective response rate and complete response rate were maintained in subgroups of patients at high risk for relapse.

Complete remissions appear to be long lasting, Schuster said.

With a median follow-up of six months since first complete remission, 24 of 29 patients (83%) who achieved complete remissions of their slow-growing lymphomas and 17 of 24 patients (71%) who achieved complete remissions of their fast-growing lymphomas remain free of disease. In some patients whose cancers progressed after receiving CAR T-cell therapy, highly sensitive molecular testing showed that the previously administered CAR T cells increased in number.

This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR-T treatment, Schuster noted.

Cytokine-release syndromeIn this study, 29% of patients treated with mosunetuzumab experienced cytokine-release syndrome that was mostly mild.

Cytokine release syndrome or CRS is caused by a large, rapid release of cytokines into the blood from immune cells affected by the immunotherapy. While most patients have a mild reaction, sometimes patients may have a severe, life threatening, reaction.

In 3% of patients, CRS was treated with tocilizumab (Actemra; Genentech/Roche). Four percent of patients experienced moderately severe neurologic side effects. Patients who received higher doses of mosunetuzumab were no more likely to have CRS or neurologic side effects than patients treated at lower doses.

A study of a higher dose of mosunetuzumab is now enrolling patients and long-term follow-up of these patients will ultimately help to better evaluate the durability of response data.

Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents, Schuster concluded.

Novel Off-the-Shelf CARPreclinical studies provide the first evidence that cellular immunotherapy for B cell cancers could ultimately become an off-the-shelf product, capable of being uniformly manufactured in large quantities as prescription drugs are.

We have taken the concept of traditional pharmaceutical drug development and applied it to cellular therapy, explained senior author Bob Valamehr, Ph.D, of Fate Therapeutics, a San Diego biopharmaceutical company.

The product called FT596, is among the first cellular immunotherapies to be based on off-the-shelf NK cells the first line of defense of the immune system and is the first cellular immunotherapy to be genetically engineered to contain three active anti-tumor components, Valamehr explained.

Comparable with standard CAR T-cell therapyFT596 demonstrated comparable ability to kill cancerous white blood cells as standard CAR T-cells and, when combined with the drug rituximab (Rituxan; Genentech/Roche), killed cancerous white blood cells that were no longer responding to standard CAR T-cell therapy due to loss of the CD19 antigen target.

The U.S. Food and Drug Administration (FDA) approved Fate Therapeutics Investigational New Drug Application for FT596 in September 2019 and the company hopes to begin a first-in-human phase I clinical trial for the treatment of B-cell lymphoma and chronic lymphocytic leukemia in the first quarter of 2020.

The primary purpose of this trial will be to assess the safety and activity of FT596 in patients.

ManufacturingThe development and manufacturing of FT596 begins with human induced pluripotent stem cells (iPSCs) that are uniquely capable of unlimited self-renewal and can differentiate into more than 200 types of human cells. These iPSCs are genetically engineered, after which a single genetically engineered cell or clone is selected and multiplied in the laboratory to create a master engineered cell line that can be repeatedly used to generate cancer-fighting immune-system cells such as NK and T cells.

Natural Kiler Cells or NK cells are a type of lymphocyte and a component of innate immune system, the bodys first line of defense against infection and disease. Unlike T-cells, which have to be trained to recognize their target and can kill only cells that display that target on their surface, NK cells do not need special preparation before going on the attack and can kill many different types of transformed or infected cells.

NK cells are multifaceted and can be viewed as a jack-of-all-trades when it comes to protecting the host, whereas T cells can act in only one way, Valamehr explained.

But NK cells are also different in other ways. They are inherently limited in their capacity to multiply and expand when infused into patients, and they have a shorter lifespan.

Valamehr and his colleagues used genetic engineering to address these shortcomings. In addition to engineering FT596 to carry a CAR targeting the CD19 protein, which is produced by nearly all B-cell lymphomas and leukemias, they inserted two other novel proteins: CD16, which boosts and broadens the NK cells ability to kill cancer cells, and IL15, which stimulates FT596 to proliferate and persist.

Valamehr explained that FT596 has been designed to address two more limitations of CAR T-cell therapy .

The investigational agent is an off-the-shelf product. As a result, it significantly improves the current patient-by-patient CAR T-cell treatment paradigm by eliminating the time-consuming and costly process that is currently required to treat a patient with CAR T-cells.

The addition of the CD16 protein gives FT596 broader therapeutic activity and versatility. In combination with rituximab, FT596 has the potential to lead to deeper and more durable responses and overcome resistance that hampers the long-term efficacy of CAR T-cell therapy.

Eliminating the high production cost, weeks of manufacturing time, and complex manufacturing process required for CAR T-cell therapy and replacing it with a mass-produced, off-the-shelf product, promises to expand access to effective cell-based cancer immunotherapy to many more patients who may benefit from it, Valamehr concluded.

Results from CARTITUDE-1 in R/R Multiple MyelomaPatients with multiple myeloma who had received a median of five prior therapies, and for whom standard-of-care treatments were no longer working, had a high response rate when treated with the investigational CAR T-cell therapy JNJ-68284528 (JNJ-4528), which targets BCMA, a protein commonly found on the surface of multiple myeloma cancer cells.

These patients participated in a clinical trials (NCT03548207), supported by Janssen Research & Development, designed to characterize safety of and establish the recommended Phase II dose (RP2D) (Phase Ib) and to evaluate the efficacy of JNJ-68284528 (Phase II).

We are seeing a high response rate, with most patients achieving MRD negativity, noted lead study author Deepu Madduri, MD, of The Tisch Cancer Institute at Mount Sinai in New York.

Considering these patients have all received multiple prior therapies, these results are extremely encouraging, Madduri added.

All evaluable patients receiving this CAR T-cell therapy have achieved MRD-negative disease state and 27 of 29 patients are progression free at a median follow-up of six months, Madduri said.

Multiple myeloma is a cancer of plasma cells, which are found in the bone marrow and are part of the immune system, the bodys defense system against infection. Typical signs and symptoms of multiple myeloma may be bone pain or fractures, high levels of calcium in the blood, kidney damage, and anemia. Multiple myeloma affects an estimated 160,000 people each year, occurs most often in people over 60. The disease is slightly more common in men than in women.

Although new therapies for multiple myeloma have recently become available that can extend patients life expectancy, a cure for the disease remains elusive.

We can get the disease into remission, but most patients unfortunately relapse, and outcomes are very poor for patients who have relapsed multiple times, she said.

Researchers explained that JNJ-4528 is a novel CAR T-cell therapy featuring two molecules that bind to BCMA, a protein found on the surface of multiple myeloma cells.

We are learning that every CAR T-cell therapy is different, Madduri said.

JNJ-4528 has a unique CAR T-cell composition in patients, preferentially enriched in CD8 T cells, which are believed to be one of the most important T cells in killing cancer cells, she noted.

This phase Ib/II trial is continuing to enroll patients.

During the 2019 annual meeting of the American Society of Hematology, Madduri reported results for the first 29 patients enrolled.

Patients T-cells were collected and sent to a laboratory where they were genetically engineered to express JNJ-4528. Prior to re-infusing these CAR T-cells, the patients received three days of chemotherapy to make room in their immune systems for the engineered T-cells.

Following chemotherapy, each patient received a single infusion of the JNJ-4528 CAR T-cells.

After a minimum of 28 days, these patients had blood and bone marrow exams, which was followed by exams at six months, and one year after treatment to assess their response. The primary aims of the trial are to assess the therapys safety and to confirm the dose to be tested in a larger, phase II trial.

The median follow-up time in the current analysis is six months. Overall, 100% of patients had a clinical response to JNJ-4528. Moreover, 66% had a stringent complete response, meaning that sensitive laboratory and microscopic tests found no evidence for myeloma proteins or cells in blood, urine, or bone marrow.

Most patients (93%) experienced some form of CRS. One patient had severe (grade 3) CRS, and one patient died from its complications 99 days after the CAR T-cell infusion. In 76% of patients, CRS was treated with tocilizumab.

To see some patients in this heavily pretreated population surviving for a year or more with a one-time treatment and a manageable safety profile is remarkable, Madduri explained.

These patients feel that they have their quality of life back. They no longer have to come into the clinic for weekly treatments and some are well enough to travel, Madduri concluded.

The phase II portion of this study is ongoing to evaluate the overall response rate of patients treated with JNJ-68284528 (JNJ-4528). Additional clinical studies are evaluating the safety and efficacy of JNJ-4528 in different multiple myeloma treatment settings.

BreakthroughEarlier this week the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for JNJ-68284528 (JNJ-4528).

The granting of Breakthrough Therapy Designation for JNJ-68284528 (JNJ-4528) is a significant milestone as we continue to accelerate the global development of this innovative CAR-T therapy in collaboration with Legend Biotech, noted Sen Zhuang, MD, Ph.D., Vice President, Oncology Clinical Development, Janssen Research & Development.

We look forward to continuing to work closely with the U.S. Food and Drug Administration to advance the clinical development program for JNJ-68284528 (JNJ-4528) and ultimately bring this BCMA-targeted immunotherapy to patients living with multiple myeloma who are in need of a new therapeutic option, Zhuang concluded.

Encouraging Results for Dual-Targeted CAR T-Cell TherapyMore than three out of four patients with multiple myeloma that returned or did not respond to at least two therapies remained in remission seven months after treatment with a novel CAR T-cell therapy targeting two proteins that are frequently found on myeloma cells.

Nine patients experiencing sustained remissions in this study, which ws supported by the National Natural Science Foundation of China, the Major Technological Innovation Special Project fund of Hubei Province of China, and Cellyan Therapeutics, were diagnosed with a difficult-to-treat form of multiple myeloma in which the disease has spread beyond the bone marrow.

Roughly one in 10 patients with multiple myeloma develop tumors in the organs or soft tissues such as the blood vessels, muscles, and nerves. These so-called extramedullary tumors respond poorly to treatment, and patients who develop them have a poor outlook and poor health related quality of life (hrQoL)

Our results show that this CAR T-cell product can effectively achieve elimination of extramedullary tumors, said study author Yu Hu, MD, Ph.D, of Union Hospital, Huazhong University of Science and Technology in Wuhan, China.

Although these are preliminary data, they are encouraging for patients with multiple myeloma who have not responded to other therapies, Hu added.

Hu and his colleagues are developing the first CAR T-cell therapy to be genetically engineered to target BCMA and CD38, two proteins found on the surface of plasma cells. Multiple myeloma is a cancer of plasma cells, which are found in the bone marrow and are part of the immune system, the bodys defense system against infection and disease.

Our thinking was that targeting both of these proteins would improve treatment efficacy without increasing toxicity, and induce deeper, more durable remissions, Hu noted.

The first-in-humans phase I trial enrolled 22 patients whose average age was 59, of whom 11 were men. All had multiple myeloma that had returned or not responded to at least three therapies. Nine of the 22 patients had extramedullary tumors. The study aims were to determine the safest and most effective dose of the CAR T-cell therapy as well as to initially evaluate its effectiveness.

Just like in other trials with CAR T-cell therapies, the participating patients received three days of chemotherapy to make room in their immune systems for the engineered T-cells. Then each patient was infused with the dual-targeted CAR T cells. Patients were divided into five groups, with each group receiving a higher dose than the previous one. Depending on the cell dose, patients received either one or two infusions.

At a median of 36 weeks of follow-up, 18 patients (90.9%) had MRD-negative disease. Twelve patients (54.5%) had a stringent complete response, meaning that no plasma cells were detected in the bone marrow. Seven patients (31.8%) had a good or very good partial response, meaning that the level of M-protein (an abnormal protein produced by cancerous plasma cells) in the blood or urine was reduced but still detectable. In eight of the nine patients with extramedullary lesions, these tumors were undetectable on their computed tomography scans. For the 17 patients who remained in remission at seven months after treatment, the median duration of response was 28.8 weeks.

The adverse events observed included 20 patients who experienced CRS, of whom six needed treatment. No serious adverse neurologic effects such as seizures, movement impairment, difficulty speaking or understanding speech, or fatal swelling in the brain were reported.

With this dual-targeted CAR T-cell therapy, we have demonstrated a high response rate, especially a higher rate and longer duration of stringent complete response, compared with other therapies, as well as effective elimination of extramedullary lesions, with no serious neurologic adverse effects and manageable levels of other adverse effects, Hu concluded.

The investigators continue to follow the patients for the next two years. They are also planning to conduct a phase II trial in both China and the United States to test the treatments effectiveness in a larger number of patients.

Clinical trialsA Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1) NCT03548207

References[1] Srivastava S, Riddell SR. Chimeric Antigen Receptor T Cell Therapy: Challenges to Bench-to-Bedside Efficacy. J Immunol. 2018;200(2):459468. doi:10.4049/jimmunol.1701155 [Abstract][2] Schuster SJ, Bartlett NL, Assouline S, Yoon SS, Bosch F, Sehn LH, Cheah CY, Shadman M, et al. Mosunetuzumab Induces Complete Remissions in Poor Prognosis Non-Hodgkin Lymphoma Patients, Including Those Who Are Resistant to or Relapsing After Chimeric Antigen Receptor T-Cell (CAR-T) Therapies, and Is Active in Treatment through Multiple Lines. 61st annual meeting of the American Society of Hematology. Program: General Sessions. Session: Plenary Scientific Session. Hematology Disease Topics & Pathways: antibodies, Follicular Lymphoma, CRS, Diseases, Biological, Therapies, neurotoxicity, Adverse Events, CAR-Ts, Non-Hodgkin Lymphoma, DLBCL, immunotherapy, Lymphoid Malignancies. [Abstract][3] Goodridge JP, Mahmood S, Zhu H, Gaidarova S, Blum R, Bjordahl R, Cichocki F, et al. FT596: Translation of First-of-Kind Multi-Antigen Targeted Off-the-Shelf CAR-NK Cell with Engineered Persistence for the Treatment of B Cell Malignancies. 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral. Session: 625. Lymphoma: Pre-ClinicalChemotherapy and Biologic Agents: Targeting Apoptosis Pathways in Lymphoma.[Abstract][4] Madduri D, Usmani SZ, Jagannath S, Singh I, Zudaire E, Yeh TM, Allred AJ, Banerjee A, et al. Results from CARTITUDE-1: A Phase 1b/2 Study of JNJ-4528, a CAR-T Cell Therapy Directed Against B-Cell Maturation Antigen (BCMA), in Patients with Relapsed and/or Refractory Multiple Myeloma (R/R MM). 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral Session: 653. Myeloma: Therapy, excluding Transplantation: Novelty in CAR T in Relapsed/Refractory Multiple Myeloma. [Abstract][5] Li C, Mei H, Hu Y, Guo T, Liu L, Jiang H, Tang L, Wu Y, et al. A Bispecific CAR-T Cell Therapy Targeting Bcma and CD38 for Relapsed/Refractory Multiple Myeloma: Updated Results from a Phase 1 Dose-Climbing Trial61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral. Session: 653. Myeloma: Therapy, excluding Transplantation: Novel Therapy for Relapsed Myeloma. Hematology Disease Topics & Pathways: Biological, Diseases, Adult, Therapies, Lymphoma (any), Adverse Events, CAR-Ts, Elderly, Biological Processes, Technology and Procedures, Cell Lineage, Study Population, Clinically relevant, Lymphoid Malignancies.

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ASH 2019: Second-gen CAR T-Cell Therapy Overcome Resistance, Reduce Toxicity and Simplify Treatment - OncoZine

Bone Marrow Stem Cells Comments Off on ASH 2019: Second-gen CAR T-Cell Therapy Overcome Resistance, Reduce Toxicity and Simplify Treatment – OncoZine | December 9th, 2019

Investor call to be held December 9 at 8:30 am ET / 1:30 pm GMT to review data

LONDON, Dec. 07, 2019 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc (Nasdaq: AUTL) announced today new data highlighting progress on its next-generation programmed T cell therapies to treat patients with acute lymphoblastic leukemia (ALL) and adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL). The data were presented in oral presentations at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, FL. Additional data on pediatric patients with ALL will be presented on December 8.

The data on AUTO1 presented at this years ASH meeting demonstrate the favorable safety profile and high level of clinical activity of AUTO1 in both adults and pediatric patients with ALL, and we look forward to initiation of the pivotal program in adult ALL in the first half of 2020, said Dr. Christian Itin, chairman and chief executive officer of Autolus.

Acute Lymphoblastic Leukemia Data Presented

Title: AUTO1 A novel fast off CD19CAR delivers durable remissions and prolonged CAR T cell persistence with low CRS or neurotoxicity in adult ALL (Abstract # 226)

Updated results for ALLCAR19, the Phase 1 trial evaluating AUTO1 in adults with recurrent/refractory ALL, were presented by Dr. Claire Roddie MB, PhD, FRCPath, honorary senior lecturer, Cancer Institute, University College London (UCL), in an oral presentation. The trial is designed to assess the primary endpoints of safety ( Grade 3 toxicity) and feasibility of product generation, as well as other secondary endpoints, including efficacy. The trial enrolled patients with a high tumor burden (44% had 50% BM blasts), who were considered high-risk for experiencing cytokine release syndrome (CRS). Product was manufactured for 19 patients; product for 13 of those patients was manufactured using a semi-automated closed process, which will be used for commercial supply.

As of the data cut-off date of November 25, 16 patients had received at least one dose of AUTO1. AUTO1 was well tolerated, with no patients experiencing Grade 3 CRS, and 3 of 16 patients (19%), who had high leukemia burden, experiencing Grade 3 neurotoxicity that resolved swiftly with steroids.

Of 15 patients evaluable for efficacy, 13 (87%) achieved MRD negative CR at 1 month and all patients had ongoing CAR T cell persistence at last follow up. CD19-negative relapse occurred in 22% (2 of 15) patients. In the patients dosed with AUTO1 manufactured in the closed process, 9 of 9 (100%) achieved MRD negative CR at 1 month and 6 months event free survival, and overall survival in this cohort was 100%.

Adult ALL patients, who face a median survival of less than one year after their ALL recurs or relapses, have a significant need for a CAR T cell therapy that is highly active, safe and is a standalone therapy not requiring a stem cell transplant, said Dr. Hagop M. Kantarjian, Chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center.

The novel CD 19 CAR-T therapy, AUTO1, is potentially transformative as a standalone curative option for patients with r/r ALL, especially in adults, given its favorable safety profile, said Dr. Max Topp associate professor of Internal Medicine, Hematology and Oncology at the University of Wuerzburg.

Title: Therapy of pediatric B-ALL with a lower affinity CD19 CAR leads to enhanced expansion and prolonged CAR T cell persistence in patients with low bone marrow tumor burden, and is associated with a favorable toxicity profile (Abstract # 225)

Dr. Sara Ghorashian, honorary senior lecturer, Great Ormond Street Institute of Child Health, University College London, presented updated data from the phase 1 CARPALL study of AUTO1 in pediatric ALL patients with low bone marrow tumor burden. The trial is intended to assess the primary endpoints of safety and proportion of patients in molecular complete remission at 1 month. The study recruited a total of 25 patients and stratified them into 2 cohorts. Fourteen patients were treated in cohort 1, which utilized a manual manufacturing process; product was unable to be generated in 3 patients. Median follow-up was 27 months in cohort 1. Seven patients were treated in cohort 2, which utilized the semi-automated closed manufacturing process, which will be used for commercial supply. The aim of cohort 2 was to demonstrate feasibility of manufacture at scale. Product was generated for 100% of patients. Median follow-up was 7 months in cohort 2.

AUTO1 was well-tolerated overall, with no patients experiencing Grade 3 CRS and 1 of 21 (5%) experiencing Grade 4 neurotoxicity, which was considered unrelated to CAR T therapy.

Nineteen of 21 treated patients (90%) achieved molecular complete remission at 1 month post infusion. Consistent with pre-clinical data, CAR T cell expansion was excellent and detectable by flow in a number of patients up to 36 months. Persistence was noted in 15 of 21 patients at last follow-up, up to 36 months. In cohort 2, 100% of patients achieved molecular complete remission at 1 month post infusion.

In the 14 patients in cohort 1, the overall survival at 6 months was 86% and at 12 months was 71%; event free survival (EFS) at 6 months was 71% and at 12 months was 54%. The patients in cohort 2 are not yet evaluable for these parameters. Overall, nine patients relapsed; 5 of 8 evaluable relapses were due to loss of CD19 antigen on the tumor cells.

Title: Clonal dynamics of early responder and long-term surviving CAR-T cells in humans (Abstract # 52)

Dr. Luca Biasco, senior research associate at University College London, presented a detailed analysis of CAR T products, and insertion site analysis from the CARPALL phase 1 patients. This analysis revealed highly polyclonal engraftment, even at very late time-points. Dr. Biasco hypothesized that the propensity for high level polyclonal long-term engraftment was due to favorable phenotype of the CAR T product and the binding kinetic of the receptor.

Diffuse Large B-cell Lymphoma Data Presented

Title: Phase 1/2 study of AUTO3, the first bicistronic chimeric antigen receptor (CAR) targeting CD19 and CD22 followed by an anti-PD1 in patients with relapsed/refractory (r/r) Diffuse Large B Cell Lymphoma (DLBCL): Results of cohort 1 and 2 of the ALEXANDER study (Abstract # 246)

Dr. Kirit Ardeshna, consultant hematologist, Department of Hematology, University College London Hospital NHS Foundation Trust, presented updated data from the ALEXANDER Phase 1/2 study of AUTO3, the first bicistronic CAR T targeting CD19 and CD22 followed by an anti-PD1, in diffuse large B cell lymphoma (DLBCL). 16 patients were treated, and fourteen patients were evaluable at one month. AUTO3 was well-tolerated, with no patients experiencing Grade 3 CRS with primary treatment, and 1 of 14 experiencing Grade 3 neurotoxicity that resolved swiftly with steroids. Five of 14 had a complete response, with 4 of 5 complete responses ongoing, the longest at 18 months.

DLBCL is an aggressive and rapidly progressing cancer, and early response is critical to ensuring positive outcomes for these patients. These early data show the promise of AUTO3 in DLBCL, and we expect to advance AUTO3 to a decision point in relapsed/refractory DLBCL by the middle of next year, said Dr. Christian Itin, chairman and chief executive officer of Autolus. In addition, we look forward to presenting the data from the AMELIA trial of AUTO3 in pediatric ALL during poster sessions on Sunday, December 8, 6:00 8:00 PM ET.

Investor call to review data on Monday, December 9

Autolus management will host an investor conference call on Monday, December 9, at 8:30 a.m. EDT/ 1:30pm GMT, to review the data presented at ASH.

To listen to the webcast and view the accompanying slide presentation, please go to: https://www.autolus.com/investor-relations/news-and-events/events.

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 9796038. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 9796038.

About AUTO1

AUTO1 is a CD19 CAR T cell investigational therapy designed to overcome the limitations in safety - while maintaining similar levels of efficacy - compared to current CD19 CAR T cell therapies. Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, AUTO1 may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the T cells' abilities to engage in serial killing of target cancer cells. In 2018, Autolus signed a license agreement under which Autolus acquired global rights from UCL Business plc (UCLB), the technology-transfer company of UCL, to develop and commercialize AUTO1 for the treatment of B cell malignancies. AUTO1 is currently being evaluated in two Phase 1 studies, one in pediatric ALL and one in adult ALL.

About AUTO3

AUTO3 is a programmed T cell therapy containing two independent chimeric antigen receptors targeting CD19 and CD22 that have each been independently optimized for single target activity. By simultaneously targeting two B cell antigens, AUTO3 is designed to minimize relapse due to single antigen loss in patients with B cell malignancies. AUTO3 is currently being tested in pediatric ALL in the AMELIA clinical trial and in diffuse large B cell lymphoma in the ALEXANDER clinical trial.

About Autolus Therapeutics plc

Autolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information please visit http://www.autolus.com.

Forward-Looking Statement

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding Autolus financial condition and results of operations, as well as statements regarding the anticipated development of Autolus product candidates, including its intentions regarding the timing for providing further updates on the development of its product candidates, and the sufficiency of its cash resources. Any forward-looking statements are based on management's current views and assumptions and involve risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in such statements. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section titled "Risk Factors" in Autolus' Annual Report on Form 20-F filed on November 23, 2018 as well as discussions of potential risks, uncertainties, and other important factors in Autolus' future filings with the Securities and Exchange Commission from time to time. All information in this press release is as of the date of the release, and the company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law.

Investor and media contact: Silvia TaylorVice President, Corporate Affairs and CommunicationsAutolus+1-240-801-3850s.taylor@autolus.com

UK:Julia Wilson+44 (0) 7818 430877j.wilson@autolus.com

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Autolus Therapeutics Announces New Data Showcasing Clinical Progress of Programmed T Cell Therapy Pipeline in Blood Cancers - BioSpace

Bone Marrow Stem Cells Comments Off on Autolus Therapeutics Announces New Data Showcasing Clinical Progress of Programmed T Cell Therapy Pipeline in Blood Cancers – BioSpace | December 9th, 2019

In 2019, the market size of Hematopoietic Stem Cell Transplantation (HSCT) is million US$ and it will reach million US$ in 2025, growing at a CAGR of from 2019; while in China, the market size is valued at xx million US$ and will increase to xx million US$ in 2025, with a CAGR of xx% during forecast period.

In this report, 2018 has been considered as the base year and 2019 to 2025 as the forecast period to estimate the market size for Hematopoietic Stem Cell Transplantation (HSCT).

Get a Sample PDF at:https://www.researchmoz.us/enquiry.php?type=S&repid=2276986

This report studies the global market size of Hematopoietic Stem Cell Transplantation (HSCT), especially focuses on the key regions like United States, European Union, China, and other regions (Japan, Korea, India and Southeast Asia).This study presents the Hematopoietic Stem Cell Transplantation (HSCT) sales volume, revenue, market share and growth rate for each key company, and also covers the breakdown data (sales, revenue and market share) by regions, type and applications. history breakdown data from 2014 to 2019, and forecast to 2025.For top companies in United States, European Union and China, this report investigates and analyzes the production, value, price, market share and growth rate for the top manufacturers, key data from 2014 to 2019.

In global market, the following companies are covered:Regen Biopharma IncChina Cord Blood CorpCBR Systems IncEscape Therapeutics IncCryo-Save AGLonza Group LtdPluristem Therapeutics IncViaCord Inc

Market Segment by Product TypeAllogeneicAutologous

Market Segment by ApplicationPeripheral Blood Stem Cells Transplant (PBSCT)Bone Marrow Transplant (BMT)Cord Blood Transplant (CBT)

Key Regions split in this report: breakdown data for each region.United StatesChinaEuropean UnionRest of World (Japan, Korea, India and Southeast Asia)

The study objectives are:To analyze and research the Hematopoietic Stem Cell Transplantation (HSCT) status and future forecast in United States, European Union and China, involving sales, value (revenue), growth rate (CAGR), market share, historical and forecast.To present the key Hematopoietic Stem Cell Transplantation (HSCT) manufacturers, presenting the sales, revenue, market share, and recent development for key players.To split the breakdown data by regions, type, companies and applicationsTo analyze the global and key regions market potential and advantage, opportunity and challenge, restraints and risks.To identify significant trends, drivers, influence factors in global and regionsTo analyze competitive developments such as expansions, agreements, new product launches, and acquisitions in the market

Inquire More About This Report @https://www.researchmoz.us/enquiry.php?type=E&repid=2276986

In this study, the years considered to estimate the market size of Hematopoietic Stem Cell Transplantation (HSCT) are as follows:History Year: 2014-2018Base Year: 2018Estimated Year: 2019Forecast Year 2019 to 2025

For More Information Kindly Contact:ResearchMozMr. Nachiket Ghumare,90 State Street,Albany NY,United States 12207Tel: +1-518-621-2074USA-Canada Toll Free: 866-997-4948Email:sales@researchmoz.usFollow us on LinkedIn @http://bit.ly/1TBmnVGMedia Release:https://www.researchmoz.us/pressreleaseFollow me on :http://marketresearchlatestreports.blogspot.com/

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Hematopoietic Stem Cell Transplantation (HSCT) Market Global Industry Study, Trends, Overview, Insights And Outlook 2019-2025 - Markets Gazette 24

Bone Marrow Stem Cells Comments Off on Hematopoietic Stem Cell Transplantation (HSCT) Market Global Industry Study, Trends, Overview, Insights And Outlook 2019-2025 – Markets Gazette 24 | December 9th, 2019

BOSTON, Dec. 09, 2019 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate mutant tumor suppressor protein p53, presented results at the 2019 ASH Annual Meeting from its U.S. Phase Ib/II clinical trial in MDS and AML. The trial is evaluating the safety and efficacy of APR-246 in combination with azacitidine for the treatment of TP53 mutated MDS and AML. The clinical trial is sponsored by the Moffitt Cancer Center with financial support from the MDS Foundation and the Aplastic Anemia and MDS International Foundation as administrator for the Evans MDS Clinical Research Consortium.

As of the data cutoff, the overall response rate (ORR) in 33 evaluable MDS patients was 88%, with a 61% complete remission (CR) rate, by International Working Group (IWG) criteria. With a median duration of follow-up of 10.8 months, the median duration of response was 8.4 months and the median duration of CR was 7.3 months. Seventeen (52%) evaluable MDS patients discontinued therapy to pursue stem cell transplant. Median overall survival (OS) for all enrolled patients (n=55) was 10.8 months. Median OS in responding patients versus non-responders was 13.7 vs. 3.9 months. Adverse events, regardless of causality, were mostly grade 1/2. Grade 3+ adverse events occurring in 20% of patients were limited to cytopenias and infection, consistent with underlying hematopoietic malignancies, and no exacerbation of the expected AZA-related safety profile has been observed.

About the Clinical Trial

Eligible patients in the Phase Ib/II clinical trial include HMA-nave, TP53 mutated MDS, oligoblastic acute myeloid leukemia (AML, 30% blasts), MDS-myeloproliferative neoplasm (MDS-MPN) overlap and chronic myelomonocytic leukemia (CMML). In the Phase Ib part of the clinical trial, patients received APR-246 in a 3+3 dose escalation design (50, 75, 100 mg/kg lean body weight) IV daily over 4 days in a lead-in phase (days -14 to -10), followed by the same dose of APR-246 (days 1-4) and AZA 75 mg/m2 SC/IV daily for 7 days (days 4-10 or 4-5 and 8-12) in 28-day cycles. In the Phase II part of the clinical trial, patients receive APR-246 as a 4,500 mg fixed dose IV daily (days 1-4) and AZA daily for 7 days (days 4-10 or 4-5 and 8-12) in 28-day cycles. Primary objective in Phase Ib part of the clinical trial was safety, with AEs graded by CTCAE v4.03 and DLT assessment over 6 weeks. Secondary endpoints included response rate by IWG 2006 criteria, PFS, OS, as well as serial next generation sequencing and p53 immunohistochemistry for evaluation of clonal suppression and depth of remission. In the Phase II part of the clinical trial the primary endpoint is CR rate.

About Myelodysplastic Syndrome

Myelodysplastic syndromes (MDS) represents a spectrum of hematopoietic stem cell malignancies in which bone marrow fails to produce sufficient numbers of healthy blood cells. Approximately 30-40% of MDS patients progress to acute myeloid leukemia (AML) and mutation of the p53 tumor suppressor protein is thought to contribute to disease progression. Mutations in p53 are found in up to 20% of MDS and AML patients and are associated with poor overall prognosis.

About p53 and APR-246

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer, occurring in approximately 50% of all human tumors. These mutations are often associated with resistance to anti-cancer drugs and poor overall survival, representing a major unmet medical need in the treatment of cancer.

APR-246 is a small molecule that has demonstrated reactivation of mutant and inactivated p53 protein by restoring wild-type p53 conformation and function and thereby induce programmed cell death in human cancer cells. Pre-clinical anti-tumor activity has been observed with APR-246 in a wide variety of solid and hematological cancers, including MDS, AML, and ovarian cancer, among others. Additionally, strong synergy has been seen with both traditional anti-cancer agents, such as chemotherapy, as well as newer mechanism-based anti-cancer drugs and immuno-oncology checkpoint inhibitors. In addition to pre-clinical testing, a Phase I/II clinical program with APR-246 has been completed, demonstrating a favorable safety profile and both biological and confirmed clinical responses in hematological malignancies and solid tumors with mutations in the TP53 gene.

A pivotal Phase 3 clinical trial of APR-246 and azacitidine for frontline treatment of TP53 mutant MDS is ongoing. APR-246 has received Orphan Drug and Fast Track designations from the FDA for MDS, and Orphan Drug designation from the EMA for MDS, AML and ovarian cancer.

About Aprea Therapeutics

Aprea Therapeutics Inc., (NASDAQ: APRE) is a biopharmaceutical company headquartered in Boston, Massachusetts with research facilities in Stockholm, Sweden, focused on developing and commercializing novel cancer therapeutics that reactivate mutant tumor suppressor protein, p53. The Companys lead product candidate is APR-246, a small molecule in clinical development for hematologic malignancies, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). For more information, please visit the company website at http://www.aprea.com.

The Company may use, and intends to use, its investor relations website at http://www.ir.aprea.com as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD.

The Company will host a 2019 ASH Clinical Update meeting and webcast as follows:

Time and Date: Monday, December 9 at 12:00 pm ETLocation: Hyatt Regency Orlando, Rainbow Spring 2 Room, 9801 International Drive, Orlando, FloridaWebcast: The Clinical Update meeting will be webcast live and can be accessed from "Events Calendar" in the News and Events section of the company's website at LinkPresentation: The presentation will be available as a PDF on the Companys website at Link

Forward-Looking Statements

Certain information contained in this press release includes forward-looking statements, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, related to our clinical trials and regulatory submissions. We may, in some cases use terms such as predicts, believes, potential, continue, anticipates, estimates, expects, plans, intends, may, could, might, likely, will, should or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team that involve risks, potential changes in circumstances, assumptions, and uncertainties. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including risks related to the success and timing of our clinical trials or other studies and the other risks set forth in our filings with the U.S. Securities and Exchange Commission, including our Quarterly Report on Form 10-Q. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances.

Corporate Contacts:

Christian S. Schade

President and Chief Executive Officer

chris.schade@aprea.com

Gregory A. Korbel

Vice President of Business Development

greg.korbel@aprea.com

Source: Aprea Therapeutics, Inc.

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Aprea Therapeutics Presents Results From U.S. Phase Ib/II Clinical Trial of APR-246 and Azacitidine (AZA) in Patients with TP53 Mutant Myelodysplastic...

Bone Marrow Stem Cells Comments Off on Aprea Therapeutics Presents Results From U.S. Phase Ib/II Clinical Trial of APR-246 and Azacitidine (AZA) in Patients with TP53 Mutant Myelodysplastic… | December 9th, 2019

Rockville, MD, Dec. 09, 2019 (GLOBE NEWSWIRE) --

MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, today announced updated results from a Phase 1/2 dose expansion study of flotetuzumab, an investigational, bispecific CD123 x CD3 DART molecule in patients with primary induction failure and early relapsed acute myeloid leukemia (AML). The data were presented in an oral session at the 61st Annual Meeting of the American Society of Hematology (ASH) in Orlando, FL, taking place December 7-10, 2019.

Patients with AML who have failed primary induction therapy or relapsed early after an initial response represent a significant unmet medical need. A remission rate of 32% observed in the ongoing study of flotetuzumab in this extremely challenging patient population is noteworthy, said Geoffrey Uy, M.D., Associate Professor, Department of Medicine, Division of Oncology at the Washington University School of Medicine in St. Louis. Importantly, by implementing a lead-in dosing schedule for flotetuzumab, as well as early intervention with tocilizumab in this study, we were able to mitigate cytokine release syndrome, known to be associated with T-cell engagers.

In the Phase 1/2 (NCT02152956) open-label, dose expansion study, 30 patients classified as primary induction failure or early relapsed AML who had received a median of four prior therapies were treated with flotetuzumab at the recommended phase 2 dose (RP2D) of 500 ng/kg/day by continuous infusion. Data were reported as of the cut-off date of November 1, 2019. The study is currently ongoing, with additional patients being enrolled.

Responses, including complete remission (CR), CRh (CR with partial hematological recovery) and CRi (CR with incomplete hematological improvement) per a modified International Working Group (IWG) Response Criteria for AML, are summarized in the table below. Four responders received allogeneic hematopoietic stem cell transplantation as consolidation therapy and remain in remission after 6 to 21 months.

The most common treatment-related adverse event (TRAE) was infusion-related reaction/cytokine release syndrome (IRR/CRS) that occurred in all (30/30) patients. However, most CRS events observed were of short duration and mild to moderate (grade 1 or 2) in severity, with only one grade 3 event reported in one patient.

Based on the encouraging data from this study, and pending anticipated discussions with the FDA in the first half of 2020, we are planning for a potential registration-enabling study of flotetuzumab in this high unmet need population of patients with refractory AML, who have limited treatment options, said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics.

A separate oral presentation described translational research that showed an inflammatory (IFN--related) gene expression signature in a subset of patients with AML that correlated with a lack of response to induction chemotherapy. Furthermore, the same gene signature was associated with patients more likely to respond to flotetuzumab, supporting the mechanism being exploited by this molecule. In addition, AML patients with an immune-infiltrated tumor micro-environment show high expression of immune checkpoint molecules, including PD-L1, which provides a scientific rationale for combining flotetuzumab with checkpoint blockade as a potential mechanism for enhanced anti-leukemic activity. MacroGenics has initiated a study combining flotetuzumab with MGA012, an anti-PD-1 antibody, given the strong preclinical and translational data that indicate the combination may enhance CD123-directed T cell killing.

Flotetuzumab Presentations at ASH

Oral Presentations

Poster Presentations

These slide and poster presentations are available on the Events & Presentations page on MacroGenics' website at http://ir.macrogenics.com/events.cfm.

Conference Call & Webcast

MacroGenics management and external guest speakers will host a conference call and audio webcast today at 8:00 p.m. ET to review the flotetuzumab data presented at the ASH Annual Meeting and discuss ongoing clinical development plans.

To participate in the MacroGenics ASH 2019 Conference Call, please dial (877) 303-6253 (domestic) or (973) 409-9610 (international) five minutes prior to the start of the call and provide the Conference ID: 3625435. A listen-only slide and audio webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company's website at http://ir.macrogenics.com/events.cfm. A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company's website for 30 days.

About Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a hematopoietic stem cell malignancy characterized by differentiation arrest and uncontrolled clonal proliferation of neoplastic precursors that prevent normal bone marrow hematopoiesis. Nearly 20,000 new cases of AML are diagnosed in the U.S. each year, with a median age of 69 years at diagnosis. Approximately 40-50% of newly diagnosed patients fail to achieve a complete remission with intensive induction therapy (primary induction failure) or experience disease recurrence after a short remission duration (<6 months; early relapsed). A very small number of these patients are expected to respond to salvage therapy. In addition, although new targeted agents have been approved for the treatment of frontline or relapsed/refractory AML in recent years, approximately 50% of patients have no known targetable mutations.

About Flotetuzumab

Flotetuzumab (also known as MGD006) is a clinical-stage molecule that recognizes both CD123 and CD3. CD123, the interleukin-3 receptor alpha chain, has been reported to be over-expressed on cancer cells in AML and other hematologic malignancies. The primary mechanism of action of flotetuzumab is believed to be its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART molecule combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cancer cells.

Flotetuzumab is currently being evaluated in the U.S. and Europe in a Phase 1/2 dose expansion study designed to assess the safety, tolerability, and initial anti-leukemic activity of the molecule in patients with relapsed/refractory AML. The U.S. Food and Drug Administration has granted orphan drug designation to flotetuzumab for the treatment of AML. A Phase 1/2 study in combination with MGA012, a proprietary anti-PD-1 monoclonal antibody, in patients with relapsed/refractory AML is being conducted ex-U.S. MGA012 (also known as INCMGA00012) was exclusively licensed to Incyte Corporation in 2017 under a global collaboration and license agreement; MacroGenics retains the right to develop its pipeline molecules with MGA012. MacroGenics retains global development and commercialization rights to flotetuzumab.

About MacroGenics, Inc.

MacroGenics is a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer. The Company generates its pipeline of product candidates primarily from its proprietary suite of next-generation antibody-based technology platforms, which have applicability across broad therapeutic domains. The combination of MacroGenics' technology platforms and protein engineering expertise has allowed the Company to generate promising product candidates and enter into several strategic collaborations with global pharmaceutical and biotechnology companies. For more information, please see the Company's website at http://www.macrogenics.com. MacroGenics, the MacroGenics logo and DART are trademarks or registered trademarks of MacroGenics, Inc.

Cautionary Note on Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for the Company, including statements about the Company's strategy, future operations, clinical development of the Company's therapeutic candidates, milestone or opt-in payments from the Company's collaborators, the Company's anticipated milestones and future expectations and plans and prospects for the Company and other statements containing the words "subject to", "believe", "anticipate", "plan", "expect", "intend", "estimate", "project", "may", "will", "should", "would", "could", "can", the negatives thereof, variations thereon and similar expressions, or by discussions of strategy constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and enrollment of future clinical trials, expectations of expanding ongoing clinical trials, availability and timing of data from ongoing clinical trials, expectations for regulatory approvals, other matters that could affect the availability or commercial potential of the Company's product candidates and other risks described in the Company's filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views only as of the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so, except as may be required by law. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date hereof.

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MacroGenics Presents Flotetuzumab Data in Patients with Primary Induction Failure and Early Relapsed Acute Myeloid Leukemia at the 2019 ASH Annual...

Bone Marrow Stem Cells Comments Off on MacroGenics Presents Flotetuzumab Data in Patients with Primary Induction Failure and Early Relapsed Acute Myeloid Leukemia at the 2019 ASH Annual… | December 9th, 2019

Pigs engineered to have a small amount of monkey cells have been brought to full term and were even born alive, surviving for a few days after birth. Although the piglets died, it is claimed the experiment - performed in China - marks a major milestone for the future of lab-grown organs.

"This is the first report of full-term pig-monkey chimeras," Tang Hai of the State Key Laboratory of Stem Cell and Reproductive Biology in Beijing told New Scientist.

The research is part of an ongoing effort to develop animals - whether they are sheep or pigs - that can grow human organs we could then harvest for transplants, a process called xenogeneic organogenesis.

Research has been done on both pig and sheep embryos with transplanted human stem cells; in both cases, the embryos continued to develop until the experiment was deliberately terminated.

That's because, due to ethical concerns, these chimeras - organisms that incorporate the genetic material of another species - cannot be cultivated or studied in the later stages of embryonic development. Some scientists worry that some of the human stem cellscould end upin other parts of the animal or even in its brain, with unintended consequences.

For that reason, in this experiment the team used stem cells from crab-eating macaques (Macaca fascicularis). These were imbued with fluorescent proteins so that they would glow under fluorescent light, and derived to produce fluorescing embryonic cells.

These cells were then injected into over 4,000 five-day-old pig embryos fertilised using IVF; the modified pig embryos were subsequently implanted into sows.

This fiddly and painstaking work produced just 10 piglets that made it to full term and were born alive. And only two of these were chimeric, with between one in 1,000 and one in 10,000 functional monkey cells to pig cells.

The monkey cells had migrated to the heart, liver, lungs, spleen and skin of the piglet hosts, but were not found in other organs, such as testes and ovaries, due to the low rate of chimerism, the researchers said.

Sadly, before a week was out, the piglets died - not just the two chimeras, but the other eight normal piglets, too. Because all the pigs died, Hai told New Scientist, the cause of death likely had less to do with chimerism, and more to do with IVF - a procedure that is notoriously tricky in pigs.

The low chimerism rate is also somewhat discouraging. However, the researchers remain optimistic. Although the birth rate was low, and the pigs didn't survive, the team now has a wealth of data they can apply to future experiments.

The scientists are planning to try again, increasing the chimeric cell ratio. And they believe their data may help other scientists working in the field.

"Here, we have used monkey cells to explore the potential of reconstructing chimeric human organs in a large animal model," they wrote in their paper.

"We believe this work will facilitate the development of xenogeneic organogenesis by providing a better understanding of the processes of xenogeneic recognition, fate determination, and the proliferation and differentiation of primate stem cells during porcine development.

"The findings could pave the way toward overcoming the obstacles in the re-engineering of heterogeneous organs and achieve the ultimate goal of human organ reconstruction in a large animal."

The research has been published in Protein & Cell.

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Pig-Monkey Chimeras Have Been Brought to Term For The First Time - ScienceAlert

Skin Stem Cells Comments Off on Pig-Monkey Chimeras Have Been Brought to Term For The First Time – ScienceAlert | December 9th, 2019

ORLANDO, Fla.--(BUSINESS WIRE)--Amnion of Florida, a leading provider of alternative medicine utilizing cryopreserved placental cell allograft and advanced bioactive facial rejuvenation, is pleased to announce their vendor choice to round out regenerative anti-aging therapies.

Amnion announces a partnership with Merakris Therapeutics, LLC to advance the development of Merakris topical bioactive anti-aging hydrogel technology. Christopher Broderick, President, and Founder of Merakris Therapeutics stated, dedication to science-based outcomes is our primary focus, thus were delighted to be selected based upon our scientific approach to youth maintenance and rejuvenation technologies.

Amnion is focused on attracting women and men seeking affordable non-surgical options for youth maintenance via cell activated procedures, hair restoration, joint repair, dermal rejuvenation, and anti-aging treatments.

Our team of experienced medical professionals and aestheticians at Amnion are excited to utilize the Merakris Therapeutics product suite, including medical-grade, sterile filtered amniotic fluid serums and hydrogels at our newest Spa in Sanford, FL, said Eusebio Coterillo, President of Amnion.

In a constantly changing field, Amnion of Florida, under the guidance of the on-site medical staff, provides the highest level of quality products and procedures in cosmetic medicine. They offer cutting edge treatments that are proven by research, the use FDA cleared or registered products, and are widely published and peer endorsed.

More about Amnion of Florida

Amnion of Florida, based in Central Florida, is a leading provider of alternative medicine using cryopreserved placental cell transplants or allografts, processed from donated cellular birth tissue, which are natural alternatives to autologous regenerative medicine products. The primary function of our allogeneic regenerative treatments is to promote soft tissue joint/skin repair and regeneration mediated by growth factors and cells naturally found in placental tissue. These treatments have shown safety and efficacy in treating a variety of ailments including osteoarthritis, chronic ulcerative wounds, joint pain, skin rejuvenation, hair restoration, urinary incontinence, and ED. Learn more http://www.amnion.us.

More about Merakris Therapeutics, LLC

Merakris Therapeutics, based in Research Triangle Park, North Carolina, is focused on researching, developing, and marketing regenerative healthcare products. Merakris is pioneering commercially scalable biotherapeutic technologies derived from stem cells that have various clinical applications. Our vision is to improve global patient care and outcomes through the pioneering and innovation of acellular regenerative biotechnologies. Learn more at http://www.merakris.com.

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Top Florida Medical Spa, Amnion of Florida, Partners With Merakris Therapeutics to Advance Their Non-Surgical Treatment Options - Business Wire

Skin Stem Cells Comments Off on Top Florida Medical Spa, Amnion of Florida, Partners With Merakris Therapeutics to Advance Their Non-Surgical Treatment Options – Business Wire | December 9th, 2019

Beijing: In a world first, researchers have been able to produce pig-monkey hybrids in a Chinese laboratory, a media report said. Two piglets - having monkey tissues in their hearts, liver and skin - were born in the State Key Laboratory of Stem Cell and Reproductive Biology in Beijing but died within a week, the Mirror reported.

The announcement to this effect was made by Tang Hai. The experiment comes in the wake of Spanish scientist Juan Carlos Izpisua Belmonte's attempt to create pig-human hybrids two years ago. Tang and his team injected genetically modified monkey cells into more than 4,000 pig embryos before these were implanted into sows, the New Scientist magazine reported.

Only two of the 10 piglets thus born were hybrids - with tissues in the heart, liver, spleen, lung and skin, partly consisting of monkey cells. Experts suspected that the failure has to do with the IVF process.

Critics have now warned that the scientific development will create "disturbing" dilemmas over the ethics of human-animal hybrids. Doctor Angel Raya, director of the Barcelona Regenerative Medicine Centre, told the Spanish daily El Pais: "What happens if the stem cells escape and form human neurons in the brain of the animal? Would it have consciousness? And what happens if these stem cells turn into sperm cells?''

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Meet the world's first pig-monkey hybrid - Free Press Journal

Skin Stem Cells Comments Off on Meet the world’s first pig-monkey hybrid – Free Press Journal | December 9th, 2019

SEATTLE--(BUSINESS WIRE)--Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune/inflammatory diseases, presented Phase 1 data yesterday from the healthy volunteer study of ALPN-101, a first-in-class dual CD28/ICOS antagonist, and details on its upcoming Phase 1/2 BALANCE study of ALPN-101 in steroid-resistant or steroid-refractory acute graft-versus-host disease (GVHD) at the 61st American Society of Hematology Annual Meeting (ASH) in Orlando, FL.

Jan Hillson, MD, Senior Vice President of Clinical Development at Alpine, presented An Open Label Study of ALPN-101, a First-in-Class Dual CD28/ICOS Antagonist, in Subjects with Steroid-Resistant or Steroid-Refractory Acute Graft Versus Host Disease (BALANCE) as part of the oral session, Chemical Biology and Experimental Therapeutics: Novel Compounds and Mechanisms of Action.

Highlights included:

Despite decades of intense research, GVHD remains a major cause of morbidity and mortality after hematopoietic stem cell transplantation, commented Sophie Paczesny, MD, PhD, Professor of Immunology and Pediatrics at Indiana University School of Medicine and lead of the Biomarkers Stem Cell Transplantation Program and one of Alpine's research collaborators. Current therapies are associated with significant toxicities or are simply insufficient to control the disease. CD28 and ICOS appear to be key pathways in the pathogenesis of GVHD, and the presented data with ALPN-101 appear uniquely strong. I look forward to the BALANCE study, which may demonstrate the therapeutic potential of ALPN-101.

About Graft Versus Host Disease (GVHD)

Graft versus host disease (GVHD) is the most common life-threatening complication of a hematopoietic cell transplant. It occurs when donor cells see recipient cells as foreign and attack them. Acute GVHD typically occurs within the early weeks and months after transplant, usually involving the skin, liver, and gastrointestinal tract. GVHD patients remain at risk of organ system damage and increased mortality due to the disease and to high dose glucocorticoids.

About ALPN-101

ALPN-101 is a novel Fc fusion protein of a human inducible T cell costimulator ligand (ICOSL) variant immunoglobulin domain (vIgD), and a first-in-class therapeutic designed to inhibit simultaneously the CD28 and ICOS inflammation pathways. CD28 and ICOS are closely-related costimulatory molecules with partially overlapping roles in T cell activation likely playing a role in multiple autoimmune and inflammatory diseases. In preclinical models of graft versus host disease, inflammatory arthritis, connective tissue disease, and multiple sclerosis, ALPN-101 demonstrates efficacy superior to agents blocking the CD28 CD80/86 or ICOS - ICOSL pathways alone.

About Alpine Immune Sciences, Inc.

Alpine Immune Sciences, Inc. is committed to leading a new wave of immune therapeutics, creating potentially powerful multifunctional immunotherapies to improve patients lives via unique protein engineering technologies. Alpine has two lead programs. The first, ALPN-101 for autoimmune/inflammatory diseases, is a selective dual T cell costimulation blocker engineered to reduce pathogenic T and B cell immune responses by blocking ICOS and CD28. ALPN-101 has recently completed enrollment in a Phase 1 healthy volunteer trial. The second, ALPN-202 for cancer, is a conditional CD28 costimulator and dual checkpoint inhibitor. Alpine is backed by world-class research and development capabilities, a highly-productive scientific platform, and a proven management team. For more information, visit http://www.alpineimmunesciences.com.

Forward-Looking Statements

This release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact and include statements regarding our platform technology and potential therapies, the timing of and results from clinical trials and pre-clinical development activities, clinical and regulatory objectives and the timing thereof, expectations regarding the sufficiency of cash to fund operations, the potential efficacy, safety profile, future development plans, addressable market, regulatory success, and commercial potential of our product candidates, the timing of our public presentations and potential publication of future clinical data, the efficacy of our clinical trial designs, expectations regarding our ongoing collaborations, and our ability to successfully develop and achieve milestones in our development programs. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions and include words such as may, will, should, would, expect, plan, intend, and other similar expressions, among others. These forward-looking statements are based on current assumptions that involve risks, uncertainties, and other factors that may cause actual results, events, or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: clinical trials may not demonstrate safety and efficacy of any of our product candidates; our ongoing discovery and pre-clinical efforts may not yield additional product candidates; our discovery-stage and pre-clinical programs may not advance into the clinic or result in approved products; any of our product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; we may not achieve additional milestones in our proprietary or partnered programs; the impact of competition; adverse conditions in the general domestic and global economic markets; as well as the other risks identified in our filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof and we undertake no obligation to update forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements.

Secreted Immunomodulatory Proteins, SIP, Transmembrane Immunomodulatory Protein, TIP, Variant Ig Domain, vIgD and the Alpine logo are registered trademarks or trademarks of Alpine Immune Sciences, Inc. in various jurisdictions.

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Alpine Immune Sciences Presents ALPN-101 Phase 1 Healthy Volunteer Study Data and Details of Upcoming Phase I/II BALANCE GVHD Study at the 61st...

Skin Stem Cells Comments Off on Alpine Immune Sciences Presents ALPN-101 Phase 1 Healthy Volunteer Study Data and Details of Upcoming Phase I/II BALANCE GVHD Study at the 61st… | December 9th, 2019

The letter follows.

Dear AgeX Stockholders,

In this, our first year as a public company, we have built a foundation for a revolutionary company in the fields of cell therapy and tissue regeneration. To date, conventional pharmaceutical approaches to the chronic degenerative conditions associated with aging have provided little benefit, often only offering relief from the symptoms of disease, rather than targeting underlying disease processes. Our belief is that this is about to change through harnessing the power of new cellular and molecular technologies. We aim to lead this coming revolution with our pioneering technologies which could generate and deliver new cells to patients through our cell therapy focus, and which may reverse the age of cells already in the body through our iTR platform. We believe that our new technologies will lead to true cell regeneration and replacement to potentially cure degenerative diseases by targeting aged or damaged cells, tissues and organs.

Over the last year, we have worked hard to achieve certain goals to set the fundamental basis to create shareholder value going forward:

To optimize shareholder value, we have undertaken a strategic review of our business opportunities, and we have four key take-away messages for the coming year and beyond:

UniverCyte would potentially be game-changing for the whole cell therapy industry by allowing the transplantation of non-self, donor cells into all patients without the need for powerful immunosuppressant drugs, which are associated with serious side effects, including infections and cancers, as well as kidney and liver toxicity. The UniverCyte platform aims to utilize a proprietary, novel, modified form of the powerful immunomodulatory molecule HLA-G, which in nature seems to be a dominant player in protecting a baby from destruction by the mother's immune system during pregnancy, the only known physiological state of immune tolerance toward foreign tissue in humans.

On the other hand, our pluripotent stem cell-based PureStem platform could potentially overcome numerous industry barriers. PureStem cells would have eight potential advantages compared to other adult stem cell- or pluripotent stem cell-based therapies, including lower manufacturing costs, industrial scalability, off-the-shelf usage, high purity, non-tumorgenicity, young age (so they are not prone to the disadvantages associated with older cells), aptitude for permanent cell engraftment, and potential to manufacture any human cell type.

We have two in-house product candidates, both targeting highly prevalent diseases of old age, with a high unmet medical need, and which are for multi-billion-dollar markets. Our lead internal program going forward will be AgeX-BAT1, which is brown fat cells for the treatment of type II diabetes. The last year has seen significant investment in cell therapy product candidates for diabetes by investors and large biotech. Earlier this year, we published a paper, Clonal Derivation of White and Brown Adipocyte Progenitor Cell Lines from Human Pluripotent Stem Cells, in the peer-reviewed scientific journal Stem Cell Research & Therapy, which showed that our PureStem platform generated highly pure, identifiable and scalable brown adipose cells, expressing active adipokines. Our second internal program will be AgeX-VASC1, composed of vascular endothelial progenitor cells for tissue ischemia, such as peripheral vascular disease and potentially cardiac and CNS ischaemia. Once we have a UniverCyte-modified pluripotent stem cell cGMP master cell bank, we will re-derive universal versions of AgeX-BAT1 and AgeX-VASC1 and then work to establish proof-of-concept in animal models.

We care deeply about our mission and the needs of our stockholders. We appreciate your support and the dedication of our scientists and employees as we forge a new future for medicine. We invite you to join us for the Annual Meeting of Stockholders on Monday, December 30, 2019. For those of you who cannot attend in person, our corporate update from that meeting will be webcast for your convenience.

Sincerely,

Michael D. West, Ph.D.

Gregory Bailey, M.D.

Chief Executive Officer

Chairman of the Board

About AgeX Therapeutics

AgeX Therapeutics, Inc. (NYSE American: AGE) is focused on developing and commercializing innovative therapeutics for human aging. Its PureStem and UniverCyte manufacturing and immunotolerance technologies are designed to work together to generate highly-defined, universal, allogeneic, off-the-shelf pluripotent stem cell-derived young cells of any type for application in a variety of diseases with a high unmet medical need. AgeX has two preclinical cell therapy programs: AGEX-VASC1 (vascular progenitor cells) for tissue ischemia and AGEX-BAT1 (brown fat cells) for Type II diabetes. AgeXs revolutionary longevity platform induced Tissue Regeneration (iTR) aims to unlock cellular immortality and regenerative capacity to reverse age-related changes within tissues. AGEX-iTR1547 is an iTR-based formulation in preclinical development. HyStem is AgeXs delivery technology to stably engraft PureStem cell therapies in the body. AgeX is developing its core product pipeline for use in the clinic to extend human healthspan and is seeking opportunities to establish licensing and collaboration agreements around its broad IP estate and proprietary technology platforms.

For more information, please visit http://www.agexinc.com or connect with the company on Twitter, LinkedIn, Facebook, and YouTube.

Forward-Looking Statements

Certain statements contained in this release are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any statements that are not historical fact including, but not limited to statements that contain words such as will, believes, plans, anticipates, expects, estimates should also be considered forward-looking statements. Forward-looking statements involve risks and uncertainties. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the business of AgeX Therapeutics, Inc. and its subsidiaries, particularly those mentioned in the cautionary statements found in more detail in the Risk Factors section of AgeXs Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commissions (copies of which may be obtained at http://www.sec.gov). Subsequent events and developments may cause these forward-looking statements to change. AgeX specifically disclaims any obligation or intention to update or revise these forward-looking statements as a result of changed events or circumstances that occur after the date of this release, except as required by applicable law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20191209005356/en/

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AgeX Therapeutics Issues Year-End Letter to Shareholders - BioSpace

Cardiac Stem Cells Comments Off on AgeX Therapeutics Issues Year-End Letter to Shareholders – BioSpace | December 9th, 2019

Organ donation involves removing a healthy organ from a donor and transplanting it into the body of a recipient who has a diseased organ that has failed irreversibly. The recipients survival often depends on getting an organ transplant.

There is a large need for organs by people affected with end-stage ailments, like diseases of the liver, lung, heart and kidney. A major obstacle to treating such people is that there arent enough donated organs around the world. In many countries, including in the West, the number of patients in the waiting list for organ transplants has progressively increased compared to the number of donor organs available.

And while the number of donors per million people is very low in many parts of the world, about 20-30 per million, its many times lower than this in India: less than 0.5 donor per million. Experts have estimated that a few lakh organs are required per year in India, although no more than 2-3% of this requirement is really met. The severe shortfall may need more effective propaganda, retrieval and use of donated organs.

There are also personal, religious and cultural barriers that make it hard for people to accept the idea of organ donation. Most religions dont appear to oppose organ donation, but people are often uncertain about these recommendations and so they are reluctant to donate. Judaism and Islam prohibit the desecration of corpses and stress on a complete body, timely rituals and burial within 24 hours after death. People may not prefer to donate organs of their near and dear after death, due to the mutilating effect of dissecting the body and removing its parts.

There are often logistical issues as well. Due to a lack of awareness of the donation procedure and its consequences, most people prefer receiving organs from live, instead of recently deceased, donors.

* * *

Organ donation came to be thanks to advances in surgical procedures that allowed doctors to replace a diseased or dying organ with a healthy foreign organ. These advances reflected the rise of the exchangeability of body parts. That is, clinicians began to view the body as a collection of organs and independent entities, such that they could be removed from one body and placed in another. By contrast, the older and more traditional view of the body regarded it as a complex, indivisible whole interacting with its environment. As the idea of exchangeability gained traction, organs became commodities with market value.

Also read:The Seamy Underbelly of Organ Transplantation in India

The advent of organ transplantation was a landmark in the history of medicine. Researchers had developed transplantation surgeries for small animals such as dogs, pigs and goats well before the 20th century. The organs in the human body that doctors most transplant are the kidney, heart and liver.

Murray and Merrill performed the first kidney transplant in the 1950s, from one monozygotic twin to another. Since the twins were genetically identical, they survived and lived for eight years after the procedure.

The first heart and liver transplants were undertaken in the mid-1960s. Christian Bernard, the famous South African surgeon, performed the first heart transplant in 1967, from a 25-year-old who was brain dead after an accident and to a 50-year-old man suffering from heart failure. In the same year, other doctors performed more than 100 heart transplants around the world, but the recipients in these transplants didnt live for more than a few days after. There were problems related to the health of the transplanted organs and the aftereffects of surgery.

An American surgeon named Thomas Starzl performed the first liver transplant in the mid-1960s. The first patient died immediately and after the surgery; a few more patients who received transplanted organs also died from infections and other illnesses within a few weeks.

Corneal grafts are a very well-known and effective form of organ or tissue donation. The cornea, which is the transparent structure on the front of the eye, consists of multiple layers of cells designed to be transparent. The cornea refracts light towards the eyes lens, located just behind it. Its relatively simpler to transplant cornea because it lacks blood vessels (i.e. since one doesnt need to restore blood vessels in the grafted tissue).

Another advantage is that the cornea is in a state of immune privilege: it is relatively protected from immune responses. So persons who undergo a corneal transplant dont need lifelong treatment with systemic drugs to suppress the immune system.

Corneal donation and transplantation have continuously evolved in theory and practice, and have a high rate of success. Franz Reisinger first attempted corneal grafts in the early 19th century, trying to transplant animal corneas into humans. He failed in repeated attempts. Reisinger also coined the term keratoplasty, which means surgery to the cornea.

Also read:Why Moral Exhortations Alone Will Not Boost Organ Donation in India

Only a few years later, Samuel Bigger, an Irish surgeon, treated a gazelle that had been blinded by a corneal scar by transplanting cornea from another gazelle.

A Viennese ophthalmologist named Edward Zirm performed the first successful corneal graft between two humans in the early 20th century.

* * *

One possible reason why organ transplants often dont have long-term success is the recipient. A person who is already sick due to a failed heart or liver is not likely to respond well to major surgery, and may have difficulty recovering from it. Similarly, an older patient may not be able to withstand the effects of surgery.

Another important factor is the recipients immune system, which could reject the donated organ. In 1979, doctors who just performed a liver transplant used a drug called cyclosporine to dampen the bodys immune response and thus spare the transplanted organ from attack. This occasion was a new step in the history of liver transplants. Cyclosporine improved the survival of over 70% of patients up to at least one year after surgery, and many patients survived for up to five yrs. Doctors have followed up with newer, better drugs to improve patients health outcomes since.

A third issue relates to an ethical question that researchers have flagged: a living donor has to undergo a major surgical procedure to donate an organ, and such procedures carry their own risks. Moreover, close relatives of a patient may be under pressure to agree to donate their organs, so they may not be necessarily free to decide for themselves. Another issue regards commercialisation: its very easy to provide monetary incentives to the poor and convince them to donate an organ in return. In such circumstances, the decision to donate an organ will not have been the result of free choice where it should be.

Such a market for kidneys is all too visible in India, where one finds advertisements for the sale of kidneys with hospitals involved in the business. Often, poor people are ready to donate their organs to make a lakh or two. Apart from theft and the black market for organs, monetary compensation for organs is legal in some parts of the world.

* * *

An alternative to overcome the shortage of organs for transplants is a xenotransplant: transplanting animal organs into humans. The principal animals that can potentially donate to humans are monkeys, since theyre most closely related to humans.

However, due to differences between the sizes of monkey and human organs, researchers have also considered pigs, whose organs are closer in dimensions as well as because pigs are easy to breed. Researchers are currently exploring these procedures in experiments.

Also read:Why Does Spain Lead the World in Organ Donation?

Another alternative for intact organs is stem cells, which scientists can grow in controlled environments, such as in a laboratory, and develop into miniature organs, or organoids. Using bioengineering techniques, they removed cells from an intact organ, such as a lung or trachea, such that the cells retain a skeleton of proteins and carbohydrates. Next, they populate these cells with stem cells and maintained them in a laboratory so that different types of cells grow inside the container. For example, scientists have grown multilayered corneas in a dish using a culture of stem cells and certain biomolecules.

Such advances in preserving and engineering tissues are help plug the gap between the demand for and supply of organs.

* * *

Its very important to preserve and properly store organs to ensure theyre in the best possible condition and retain their nature following transplantation. One particular concern here stems from the time and temperature of storage, which need to be carefully controlled to remain within specific limits depending on the organ and the type of death. Maintaining the right conditions ensures the organ remains viable after the recipient has received it. A heart may be stored for up to four hours, the lungs for up to six hours and the kidneys for longer periods, up to 18 hours.

A critical question to be addressed with regard to organ donation is the distinction between brain death and cardiac, or circulatory, death. A brain-dead patient will still have a functioning heart and may be on life support. However, brain-death means brain function has been completely and irreversibly lost.

For an organ donor, a criterion of either brain death or cardiac death may be taken under the definition of death. Indian law mentions two possibilities. One is in the Registration of Births and Deaths Act and the other, in the Transplantation of Human Organs and Tissues (THOT) Act. The former defines death as the permanent disappearance of all evidence of life at any time after live-birth has taken place. The THOT Act, on the other hand, defines a deceased person as one in whom permanent disappearance of all evidence of life occurs, by reason of brain stem death or in a cardiopulmonary sense, at any time after live-birth has taken place.

In many countries, both forms of death are considered acceptable for organ donation.

Chitra Kannabiranleads research on molecular genetics at the L.V. Prasad Eye Institute, Hyderabad.

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The Ins and Outs of Organ Donation - The Wire

Cardiac Stem Cells Comments Off on The Ins and Outs of Organ Donation – The Wire | December 9th, 2019

Autologous Stem Cell and Non-Stem Cell Based Therapies Market Report 2018-2026includes a comprehensive analysis of the present Market. The report starts with the basic Autologous Stem Cell and Non-Stem Cell Based Therapies industry overview and then goes into each and every detail.

Autologous Stem Cell and Non-Stem Cell Based Therapies Market Report contains in depth information major manufacturers, opportunities, challenges, and industry trends and their impact on the market forecast. Autologous Stem Cell and Non-Stem Cell Based Therapies also provides data about the company and its operations. This report also provides information on the Pricing Strategy, Brand Strategy, Target Client, Distributors/Traders List offered by the company.

Description:

Autologous stem-cell transplantation (also known as autogeneic, autogenic, or autogenous stem-cell transplantation or auto-SCT) is the autologous transplantation of stem cellswhich is, transplantation in which the undifferentiated cells or stem cells (cells from which other types of cells develop) are taken from a person, accumulated, and given back to the same person later. Even though it is most often executed by means of hematopoietic stem cells (antecedent of cells that forms blood) in hematopoietic stem cell transplantation, in some cases cardiac cells are used productively to fix the damages due to heart attacks. Stem cell transplantation can be of two types Autologous stem-cell transplantation and allogenic stem cell transplantation. In the later, the recipient and the donor of stem cells are dissimilar people. In a good number of allogeneic transplants, the stem cells are taken from a donor whose cell type matches closely with the patients cell type.

Autologous Stem Cell and Non-Stem Cell Based Therapies Market competition by top manufacturers/players, with Autologous Stem Cell and Non-Stem Cell Based Therapies sales volume, Price (USD/Unit), Revenue (Million USD) and Market Share for each manufacturer/player; the top players including: NeoStem, Inc., Aastrom Biosciences, Fibrocell Science, Inc., Genzyme Corporation, BrainStorm Cell Therapeutics, Regeneus Ltd., and Dendreon Corporation.

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Important Features that are under offer & key highlights of the report:

What all regional segmentation covered? Can the specific country of interest be added?Currently, the research report gives special attention and focus on the following regions:North America (U.S., Canada, Mexico), Europe (Germany, U.K., France, Italy, Russia, Spain etc), South America (Brazil, Argentina etc) & Middle East & Africa (Saudi Arabia, South Africa etc)** One country of specific interest can be included at no added cost. For inclusion of more regional segment quote may vary.

What all companies are currently profiled in the report?The report Contain the Major Key Players currently profiled in this market.** List of companies mentioned may vary in the final report subject to Name Change / Merger etc.

Can we add or profiled new company as per our need?Yes, we can add or profile new company as per client need in the report. Final confirmation to be provided by the research team depending upon the difficulty of the survey.** Data availability will be confirmed by research in case of a privately held company. Up to 3 players can be added at no added cost.

Can the inclusion of additional Segmentation / Market breakdown is possible?Yes, the inclusion of additional segmentation / Market breakdown is possible to subject to data availability and difficulty of the survey. However, a detailed requirement needs to be shared with our research before giving final confirmation to the client.** Depending upon the requirement the deliverable time and quote will vary.

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Autologous Stem Cell and Non-Stem Cell Based Therapies Market Dynamics in the world mainly, the worldwide 2018-2026 Autologous Stem Cell and Non-Stem Cell Based Therapies Market is analyzed across major global regions. CMI also provides customized specific regional and country-level reports for the following areas:

Region Segmentation:

North America (USA, Canada and Mexico)Europe (Germany, France, UK, Russia and Italy)Asia-Pacific (China, Japan, Korea, India and Southeast Asia)South America (Brazil, Argentina, Columbia etc.)Middle East and Africa (Saudi Arabia, UAE, Egypt, Nigeria and South Africa)

Further in the report, the Autologous Stem Cell and Non-Stem Cell Based Therapies market is examined for Sales, Revenue, Price and Gross Margin. These points are analyzed for companies, types, and regions. In continuation with this data, the sale price is for various types, applications and region is also included. The Autologous Stem Cell and Non-Stem Cell Based Therapies industry consumption for major regions is given. Additionally, type wise and application wise figures are also provided in this report.

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In this study, the years considered to estimate the market size of 2018-2026 Autologous Stem Cell and Non-Stem Cell Based Therapies Market are as follows:History Year: 2015-2017Base Year: 2017Estimated Year: 2018Forecast Year 2018 to 2026

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Autologous Stem Cell and Non-Stem Cell Based Therapies Market share, size, opportunities, producers, growth factors by 2026 - Health Opinion

Cardiac Stem Cells Comments Off on Autologous Stem Cell and Non-Stem Cell Based Therapies Market share, size, opportunities, producers, growth factors by 2026 – Health Opinion | December 9th, 2019

A hockey player paralyzed in the Humboldt Broncos bus crash says it feels good to be home after spending five weeks in Thailand, where he underwent spinal surgery.

It feels good. I mean I felt that cold, cold wind hit my legs, so Im feeling good. Its good to be back, Ryan Straschnitzki said Sunday night as he wheeled himself into the Calgary airport.

The 20-year-old from Airdrie, Alta., who is paralyzed from the chest down, had an epidural stimulator implanted in his spine while he was in Bangkok. A week later, doctors also injected stem cells above and below his spinal injury to try to reverse some of the damage.

Videos posted by Straschnitzki and his father in Thailand show him straightening a leg. In another, Straschnitzki kicks a ball.

In another clip, while hes strapped into a harness, physiotherapists slowly help him walk with a wheeled machine.

It was incredible. I mean the last time I walked beside my dad was before the accident and before I moved away, said Straschnitzki. So doing that again and just seeing the look in his eyes is motivating to me.

Straschnitzki was one of 13 players injured when a semi truck blew through a stop sign and into the path of his junior hockey teams bus at a rural intersection in Saskatchewan in April 2018.

Sixteen others on the bus were killed.

READ MORE: Paralyzed Humboldt Broncos player to get spinal surgery in Thailand

Tom Straschnitzki said hes not an emotional guy, but watching the progress his son made in Thailand has given him hope.

When I actually saw him move his leg, it just took me back to imagining his last steps going onto that bus on that fateful day. And I was just thinking maybe he can go back on the bus one day, he said.

The surgery can cost up to $100,000 but isnt covered by public health care or insurance, because it has not been approved by Health Canada. The Straschnitzkis say theyre frustrated the treatment isnt available here.

Ryan Straschnitzki hopes his experience might at least get the conversation going.

Our health-care system is kind of lacking in this area for spinal cord injuries and I think its huge that Thailand and some other places are getting this started, he said.

I think if Canada can step in and advance this program, I think itll help a lot of people out.

Tom and Michelle Straschnitzki said they have been flooded with comments and questions about their sons procedure.

They want to try it and ask why doesnt Canada do it? I dont have the answer about Canada but they do it in Thailand and it is not experimental, said Tom Straschnitzki.

Health Canada has said it provides licensed spinal cord stimulators but only for pain relief. A spokesman said it has not received an application to have stimulators used to regain motor skills.

READ MORE: Loss for words Injured Bronco shocked, excited over effect of spinal surgery

Ryan Straschnitzki said he isnt expecting a cure but hopes his implant will restore some muscle movement.

Just getting that feeling of being able to move something that I wasnt able to move before and I know core is a huge part of my disability, so anything below my chest is crucial. And after the programming it really helped, he said.

Straschnitzki is hoping to make the Canadian sledge hockey team and compete in the Olympics. He even took his sled with him to Thailand and sat in it as part of his rehabilitation there.

He said he plans to take a few days off before returning to physiotherapy and hitting the ice again back home.

Bill Graveland, The Canadian Press

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Kind of lacking: Injured Bronco wonders why Canada wont fund spinal surgery - Coast Mountain News

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--(BUSINESS WIRE)--Jasper Therapeutics is a biotechnology company focused on enabling safer conditioning agents and therapeutics to allow for expanded use of curative hematopoietic stem cell transplants and gene therapies. Jasper Therapeutics lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a stem cell transplant. For more information, please visit us at http://www.jaspertherapeutics.com.

Company:

Jasper Therapeutics, Inc

Headquarters Address:

3000 Sand Hill Road B1-145

Menlo Park, CA

Main Telephone:

1-650-254-6687

Website:

https://jaspertherapeutics.com/

Type of Organization:

Private

Industry:

Biotechnology

Key Executives:

Executive Chairman and Interim Chief Executive Officer: William Lis

Chief Business Officer, Chief Financial Officer: Jeet Mahal

Company Contact

Contact:

Jeet Mahal

Phone:

1-650-254-6687

Email:

jmahal@jaspertherapeutics.com

Public Relations

Contact:

Julie Normart

Phone:

1-415-946-1087

Email:

jnormart@w2ogroup.com

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Company Profile for Jasper Therapeutics, Inc - Business Wire

Bone Marrow Stem Cells Comments Off on Company Profile for Jasper Therapeutics, Inc – Business Wire | December 8th, 2019

Our lives have been transformed by the information age. But what's coming next is likely to be more profound, call it the genetic information age. We have mapped the human genome and in just the last few years we have learned to read and write dna like software. And you're about to see a few breakthroughs-in-waiting that would transform human health. For a preview of this revolution in evolution we met George Church, a world leading geneticist, whose own DNA harbors many eccentricities and a few genes for genius.

We found George Church in here.Cory Smith: Most of these are frozen George. Little bits of George that we have edited all in different tubes.

Church threw himself into his work, literally. His DNA is in many of the experiments in his lab at Harvard Medical School. The fully assembled George Church is 6'5" and 65. He helped pioneer mapping the human genome and editing DNA. Today, his lab is working to make humans immune to all viruses, eliminate genetic diseases, and reverse the effects of time.

Scott Pelley: One of the things your lab is working on is reversing aging.

George Church: That's right.

Scott Pelley: How is that possible?

George Church: Reversing aging is one of these things that is easy to dismiss to say either we don't need it or is impossible or both.

Scott Pelley: Oh, we need it.

George Church: Okay. We need it. That's good. We can agree on that. Well, aging reversal is something that's been proven about eight different ways in animals where you can get, you know, faster reaction times or, you know, cognitive or repair of damaged tissues.

Scott Pelley: Proven eight different ways. Why isn't this available?

George Church: It is available to mice.

In lucky mice, Church's lab added multiple genes that improved heart and kidney function and levels of blood sugar. Now he's trying it in spaniels.

Scott Pelley: So is this gene editing to achieve age reversal?

George Church: This is adding genes. So, it's not really editing genes. It's, the gene function is going down, and so we're boosting it back up by putting in extra copies of the genes.

Scott Pelley: What's the time horizon on age reversal in humans?

George Church: That's in clinical trials right now in dogs. And so, that veterinary product might be a couple years away and then that takes another ten years to get through the human clinical trials.

Human trials of a personal kind made George Church an unlikely candidate to alter human evolution. Growing up in Florida, Church was dyslexic, with attention deficit, and frequently knocked out by narcolepsy.

Scott Pelley: What was it that made you imagine that you could be a scientist?

George Church: The thing that got me hooked was probably the New York World's Fair in 1964. I thought this is the way we should all be living. When I went back to Florida, I said, "I've been robbed," you know? "Where is it all?" So, I said, "Well, if they're not going to provide it, then I'm gonna provide it for myself."

With work and repetition, he beat his disabilities and developed a genius for crystallography, a daunting technique that renders 3D images of molecules through X-rays and math. But in graduate school at Duke, at the age of 20, his mania for the basic structures of life didn't leave time for the basic structure of life.

Scott Pelley: You were homeless for a time.

George Church: Yeah. Briefly.

Scott Pelley: Six months.

George Church: Six months.

Scott Pelley: And where were you sleeping when you were homeless?

George Church: Well, yeah. I wasn't sleeping that much. I was mostly working. I'm narcoleptic. So, I fall asleep sitting up anyway.

His devotion to crystallography was his undoing at Duke.

George Church: I was extremely excited about the research I was doing. And so, I would put in 100-plus hours a week on research and then pretty much didn't do anything else.

Scott Pelley: Not go to class.

George Church: I wouldn't go to class. Yeah.

Duke kicked him out with this letter wishing him well in a field other than biology. But, it turned out, Harvard needed a crystallographer. George Church has been here nearly 40 years. He employs around 100 scientists, about half-and-half men and women.

Scott Pelley: Who do you hire?

George Church: I hire people that are self-selecting, they see our beacon from a distance away. There are a lot of people that are a little, you know, might be considered a little odd. "Neuroatypicals," some of us are called.

Scott Pelley: "Neuroatypical?"

George Church: Right.

Scott Pelley: Unusual brains?

George Church: Right, yeah.

Parastoo Khoshakhlagh: One thing about George that is very significant is that he sees what you can't even see in yourself.

Parastoo Khoshakhlagh and Alex Ng are among the "neuroatypicals." They're engineering human organ tissue.

Cory Smith: I think he tries to promote no fear of failure. The only fear is not to try at all.

Cory Smith's project sped up DNA editing from altering three genes at a time to 13,000 at a time. Eriona Hysolli went to Siberia with Church to extract DNA from the bones of wooly mammoths. She's editing the genes into elephant DNA to bring the mammoth back from extinction.

Eriona Hysolli: We are laying the foundations, perhaps, of de-extinction projects to come.

Scott Pelley: De-extinction.

Eriona Hysolli: Yes.

Scott Pelley: I'm not sure that's a word in the dictionary yet.

Eriona Hysolli: Well, if it isn't, it should be.

Scott Pelley: You know there are people watching this interview who think that is playing God.

George Church: Well, it's playing engineer. I mean, humans have been playing engineer since the dawn of time.

Scott Pelley: The point is, some people believe that you're mucking about in things that shouldn't be disturbed.

George Church: I completely agree that we need to be very cautious. And the more powerful, or the more rapidly-moving the technology, the more cautious we need to be, the bigger the conversation involving lots of different disciplines, religion, ethics, government, art, and so forth. And to see what it's unintended consequences might be.

Church anticipates consequences with a full time ethicist in the lab and he spends a good deal of time thinking about genetic equity. Believing that genetic technology must be available to all, not just those who can afford it.

We saw one of those technologies in the hands of Alex Ng and Parastoo Khoshakhlagh. They showed us what they call "mini-brains," tiny dots with millions of cells each. They've proven that cells from a patient can be grown into any organ tissue, in a matter of days, so drugs can be tested on that patient's unique genome.

Scott Pelley: You said that you got these cells from George's skin? How does that work?

Alex Ng: We have a way to reprogram essentially, skin cells, back into a stem cell state. And we have technologies where now we can differentiate them into tissue such as brain tissue

Scott Pelley: So you went from George's skin cells, turned those into stem cells, and turned those into brain cells.

Alex Ng: Exactly. Exactly.

Scott Pelley: Simple as that.

Organs grown from a patient's own cells would eliminate the problem of rejection. Their goal is to prove the concept by growing full sized organs from Church's DNA.

George Church: It's considered more ethical for students to do experiments on their boss than vice versa and it's good to do it on me rather than some stranger because I'm as up to speed as you can be on the on the risks and the benefits. I'm properly consented. And I'm unlikely to change my mind.

Alex Ng: We have a joke in the lab, I mean, at some point, soon probably, we're going to have more of his cells outside of his body than he has himself.

Church's DNA is also used in experiments designed to make humans immune to all viruses.

George Church: We have a strategy by which we can make any cell or any organism resistant to all viruses by changing the genetic code. So if you change that code enough you now get something that is resistant to all viruses including viruses you never characterized before.

Scott Pelley: Because the viruses don't recognize it anymore?

George Church: They expect a certain code provided by the host that they replicate in. the virus would have to change so many parts of its DNA or RNA so that it can't change them all at once. So, it's not only dead. But it can't mutate to a new place where it could survive in a new host.

Yes, he's talking about the cure for the common cold and the end of waiting for organ transplants. It's long been known that pig organs could function in humans. Pig heart valves are routinely transplanted already. But pig viruses have kept surgeons from transplanting whole organs. Church's lab altered pig DNA and knocked out 62 pig viruses.

Scott Pelley: What organs might be transplanted from a pig to a human?

George Church: Heart, lung, kidney, liver, intestines, various parts of the eye, skin. All these things

Scott Pelley: What's the time horizon on transplanting pig organs into human beings?

George Church: you know, two to five years to get into clinical trials. And then again it could take ten years to get through the clinical trials.

Church is a role model for the next generation. He has co-founded more than 35 startups. Recently, investors put $100 million into the pig organ work. Another Church startup is a dating app that compares DNA and screens out matches that would result in a child with an inherited disease.

George Church: You wouldn't find out who you're not compatible with. You'll just find out who you are compatible with.

Scott Pelley: You're suggesting that if everyone has their genome sequenced and the correct matches are made, that all of these diseases could be eliminated?

George Church: Right. It's 7,000 diseases. It's about 5% of the population. It's about a trillion dollars a year, worldwide.

Church sees one of his own genetic differences as an advantage. Narcolepsy lulls him several times a day. But he wakes, still in the conversation, often, discovering inspiration in his twilight zone.

Scott Pelley: If somebody had sequenced your genome some years ago, you might not have made the grade in some way.

George Church: I mean, that's true. I would hope that society sees the benefit of diversity not just ancestral diversity, but in our abilities. There's no perfect person.

Despite imperfection, Church has co-authored 527 scientific papers and holds more than 50 patents. Proof that great minds do not think alike.

The best science can tell, it was about 4 billion years ago that self-replicating molecules set off the spark of biology. Now, humans hold the tools of evolution, but George Church remains in awe of the original mystery: how chemistry became life.

Scott Pelley: Is the most amazing thing about life, then, that it happened at all?

George Church: It is amazing in our current state of ignorance. We don't even know if it ever happened ever in the rest of the universe. it's awe-inspiring to know that it either happened billions of times, or it never happened. Both of those are mind boggling. It's amazing that you can have such complex structures that make copies of themselves. But it's very hard to do that with machines that we've built. So, we're engineers. But we're rather poor engineers compared to the pseudo engineering that is biological evolution.

Produced by Henry Schuster. Associate producer, Rachael Morehouse. Broadcast associate, Ian Flickinger.

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Each day until Christmas we'll be announcing an award winner - think of it as a virtual advent calendar. Today its the turn of Best Hair Tool - brushes at the ready

Wednesday 27 November saw some of the biggest names in beauty and wellness gather at Get The Gloss' HQ with the sole purpose of whittling down the 450 awards entries we received.

Our judges blazed through the day swatching, spritzing and swirling, putting the products through their paces, and after hours spent poring over the latest and greatest beauty releases, our panel of esteemed judges narrowed down over 450 beauty products to a shortlist and a selection of worthy winners. From cult names to little-known brands, your beauty wish list is about to get a whole lot longer.

Check back here and on our Instagram @getthegloss each day to discover our very worthy winners...

Winner: Manta x Zoe Irwin, 25

More than just a hair brush, this ergonomically shaped tool feels like a mini head massage every time you use it - our judges loved the way it stimulated the scalp in ways that other handheld brushes dont.

Commended: Hair story Brush, 11

To be used in conjunction with our Best Health Hair Saviour winner New Wash, this helps rinse hair product thoroughly, and promotes blood circulation for less hair loss, as well as effectively removing dandruff and protecting the scalp from scratchy fingernails.

Winner: ZENii Stem Cell Renewal Day Cream SPF 30, 70

As opposed to a pure SPF product this is moisturiser combined with a high SPF; its comfortable enough to wear all day, with editorial director Victoria Woodhall saying: It feels lovely, quite amazing and very soft.

While it may be expensive, the hefty price tag comes backed up with powerful ingredients including citrus stem cells and hyaluronic acid.

Commended: Altruist Sunscreen SPF50, 7.50 for 2x100ml

For such a fabulous price point, you really cant go wrong with this. Its lightweight with founder Sarah Vine commenting: Thats very nice, I would actually wear that - big words!

We like the story behind it too - the price point is so reasonable as it was launched by a dermatologist who wanted to make sunscreen accessible to all to reduce skin cancer diagnoses.

Winner: Code8 Highlight HD Palette, 24

For a touch of summer in the chilliest months, you cant go wrong with this two-toned palette, that offers the perfect amount of shimmer.

Commended: Beuti Skincare Pomegranate Glow 3in1 Enzyme Cleanser flash mask, 55.00

We love a multi-purpose product, so this was an instant hit around the judging table. The gel-balm hybrid can be used as a cleanser or a mask for a mini-facial, depending on what youre after.

Winner: WooWoo Tame it! Hair Removal Cream, 6.75

A far cry from the hair removal creams of yesteryear, this has none of the unpleasant scent you might remember and leaves skin soft and smooth. It almost makes hair removal cool - no mean feat!

Highly commended: MegsMenopause Blossom Balm, 10

Targeting vaginal dryness, this intimate skin moisturiser makes menopause a whole lot more comfortable - plus, the bottle is made from 96% recyclable materials.

Winner: Votary Rose Geranium and Apricot Cleansing Oil, 45

When Ateh Jewel says she uses a product every night, you sit up and listen. Something of a cult item in beauty circles, this cleansing oil goes on like velvet and leaves your skin feeling like silk.

Highly commended: Jane Scrivner Nourishing Cleanser, 46

With a creamy and delicious texture, this removes every scrap of makeup without being harsh on the skin.

Highly commended: PAI Light Work Rosehip Cleansing Oil, 36

As the name says, this cleansing oil is light as air, with the rosehip leaving a pleasing glow on the skin.

Winner: 001 Cryopress Ice Facial Massager, 75

After a full-on day of judging, this ice-cold facial massager was a breath of fresh air. Kept between -8 and 2.5 degrees Celcius, rolling this over your face increases blood circulation, tightening, firming and lifting the skin. Get The Gloss founder Susannah Taylor commented how amazing it made her skin feel, and if it's good enough for her...

Highly commended: Hayou Beauty Restorer, 38

This jade facial massage tool might not look like much, but it sure packs a punch. Simply sweep it over your face for a massage that not only improves circulation but can also soothe headaches and release tension. Our editorial director Victoria Woodhall commented that she loves it because it transforms your skin from the inside out.

Winner: Hairstory New Wash, 44

When a product is loved by Jonathan Van Ness, you just know it's going to be good - and our judges were definitely in agreement on this one. Darren Fowler commented that he loved the idea of a biodegradable cleanser that does everything in one - a product to use in place of shampoo which strips excess oil, dirt and styling products, but leaves behind all the goodness your hair needs to be happy and healthy.

Highly commended: L'Oreal Professionnel Vitamino Colour Shampoo, 12.90

Expert judges Cher Webb and Susannah Taylor both already use this in their day-to-day lives, so we were excited to give it a whirl - and we weren't disappointed by this trusted and well-known shampoo. Designed for coloured hair, it leaves locks shiny and vibrant, without weighing it down.

Winner: IT Cosmetics Superhero Mascara, 20

A stalwart in makeup artists' bags, Superhero Mascara boasts serious staying power, with our judges impressed by how a little goes a long way - serious bang for your buck with this one. Judge Cher Webb said she always carried it in her kit.

Highly commended: Lottie London Power Foil, 5.20

Launched in 2014, Lottie London is a relatively new player in the game. This eyeshadow wowed the panel thanks to the highly pigmented formula that creates a three-dimensional illusion on the eyes - Christmas party makeup isn't complete without it. Judge and hairstylist Darren Fowler said he'd love to see this on a model when he's on a shoot.

Watch this space tomorrow for another winner's announcement and follow us on Instagram @getthegloss for updates.

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Get The Gloss Beauty & Wellness Awards 2019: The winners & commended - Get The Gloss

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The spinal cord is a long, fragile tubelike structure that begins at the end of the brain stem and continues down almost to the bottom of the spine. The spinal cord consists of nerves that carry incoming and outgoing messages between the brain and the rest of the body. It is also the center for reflexes, such as the knee jerk reflex (see Figure: Reflex Arc: A No-Brainer).

Like the brain, the spinal cord is covered by three layers of tissue (meninges). The spinal cord and meninges are contained in the spinal canal, which runs through the center of the spine. In most adults, the spine is composed of 33 individual back bones (vertebrae). Just as the skull protects the brain, vertebrae protect the spinal cord. The vertebrae are separated by disks made of cartilage, which act as cushions, reducing the forces generated by movements such as walking and jumping. The vertebrae and disks of cartilage extend the length of the spine and together form the vertebral column, also called the spinal column.

A column of bones called vertebrae make up the spine (spinal column). The vertebrae protect the spinal cord, a long, fragile structure contained in the spinal canal, which runs through the center of the spine. Between the vertebrae are disks composed of cartilage, which help cushion the spine and give it some flexibility.

Like the brain, the spinal cord is covered by three layers of tissue (meninges).

Spinal nerves: Emerging from the spinal cord between the vertebrae are 31 pairs of spinal nerves. Each nerve emerges in two short branches (roots):

One at the front (motor or anterior root) of the spinal cord

One at the back (sensory or posterior root) of the spinal cord

The motor roots carry commands from the brain and spinal cord to other parts of the body, particularly to skeletal muscles.

The sensory roots carry information to the brain from other parts of the body.

Cauda equina: The spinal cord ends about three fourths of the way down the spine, but a bundle of nerves extends beyond the cord. This bundle is called the cauda equina because it resembles a horses tail. The cauda equina carries nerve impulses to and from the legs.

Like the brain, the spinal cord consists of gray and white matter. The butterfly-shaped center of the cord consists of gray matter. The front wings (also called horns) contain motor nerve cells (neurons), which transmit information from the brain or spinal cord to muscles, stimulating movement. The back horns contain sensory nerve cells, which transmit sensory information from other parts of the body through the spinal cord to the brain. The surrounding white matter contains columns of nerve fibers that carry sensory information to the brain from the rest of the body (ascending tracts) and columns that carry motor impulses from the brain to the muscles (descending tracts).

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Spinal Cord - Brain, Spinal Cord, and Nerve Disorders ...

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By Insoo Hyun

Stem cells are undifferentiated cells that have the capacity to renew themselves and to specialize into various cell types, such as blood, muscle, and nerve cells. Embryonic stem cells, derived from five-day-old embryos, eventually give rise to all the different cells and organ systems of the embryo. Embryonic stem cells are pluripotent, because they are capable of differentiating along each of the three germ layers of cells in the embryo, as well as producing the germ line (sperm and eggs). The three germ layers are the ectoderm (skin, nerves, brain), the mesoderm (bone, muscle), and the endoderm (lungs, digestive system).

During later stages of human development, minute quantities of more mature stem cells can be found in most tissue and organ systems, such as bone marrow, the skin, and the gut. These are somatic stem cells, responsible for renewing and repairing the bodys specialized cells. Although the lay public often refers to them as adult stem cells, researchers prefer to call them multipotent because they are less versatile than pluripotent stem cells, and because they are present from the fetal stage of development and beyond. Multipotent stem cells can only differentiate into cells related to the tissue or organ systems from which they originated for instance, multipotent blood stem cells in bonemarrow can develop into different types of blood cells, but not into nerve cells or heart cells.

While multipotent stem cell research has been around for nearly 50 years and has led to clinical therapies for leukemia and other blood disorders, the field of human embryonic stem cell research is still relatively new, and basic discoveries have yet to be directly transitioned into clinical treatments. Human embryonic stem cells were first isolated and maintained in culture in 1998 by James Thomson and colleagues at the University of Wisconsin. Since then, more than a thousand different isolateslines of self-renewing embryonic stem cellshave been created and shared by researchers worldwide.

The main ethical and policy issues with stem cells concern the derivation and use of embryonic stem cells for research. A vocal minority of Americans objects to the destruction of embryos that occurs when stem cells are derived. Embryonic stem cell research is especially controversial for those who believe that five-day-old preimplantation human embryos should not be destroyed no matter how valuable the research may be for society.

To bypass this ethical controversy, the Presidents Council on Bioethics recommended in 2005 that alternative sources of pluripotent stem cells be pursued. Some alternatives have been developed, most notably, the induced pluripotent stem (iPS) cells human skin cells and other body cells reprogrammed to behave like embryonic cells. But embryonic stem cell research will remain needed because there are some questions only they have the potential to answer.

Embryonic stem cells are necessary for several aims of scientific and biomedical research. They include addressing fundamental questions in developmental biology, such as how primitive cells differentiate into more specialized cells and how different organ systems first come into being. By increasing our knowledge of human development, embryonic stem cells may also help us better understand the causes of fetal deformations.

Other important applications lie in the areas of disease research and targeted drug development. By deriving and studying embryonic or other pluripotent stem cells that are genetically-matched to diseases such as Parkinsons disease and juvenile diabetes, researchers are able to map out the developmental course of complex medical conditions to understand how, when, and why diseased specialized cells fail to function properly in patients. Such disease-in-a-dish model systems provide researchers with a powerful new way to study genetic diseases. Furthermore, researchers can aggressively test the safety and efficacy of new, targeted drug interventions on tissue cultures of living human cells derived from disease-specific embryonic stem cells. This method of testing can reduce the risks associated with human subjects research.

One possible way of deriving disease-specific stem cells is through a technique called somatic cell nuclear transfer (SCNT), otherwise known as research cloning. By replacing the DNA of an unfertilized egg with the DNA of a cell from a patients body, researchers are able to produce embryonic stem cells that are genetically-matched to the patient and his or her particular disease. SCNT, however, is technically challenging and requires the collection of high-quality human eggs from female research volunteers, who must be asked to undergo physically burdensome procedures to extract eggs.

A much more widespread and simpler technique for creating disease-specific stem cells was pioneered in 2006 by Shinya Yamanaka and colleagues in Kyoto, Japan. They took mouse skin cells and used retroviruses to insert four genes into them to to create iPS cells. In 2007, teams led by Yamanaka, James Thomson, and George Daley each used similar techniques to create human iPS cells. The iPS cell approach is promising because disease-specific stem cells could be created using skin or blood samples from patients and because, unlike SCNT, it does not require the procurement of human eggs for research.

However, despite these advances, scientists do not believe iPS cells can replace human embryonic stem cells in research. For one, embryonic stem cells must be used as controls to assess the behavior and full scientific potential of iPS cells. Furthermore, iPS cells may not be able to answer some important questions about early human development. And safety is a major issue for iPS cell research aimed at clinical applications, since the cell reprogramming process can cause harmful mutations in the stem cells, increasing the risk of cancer. In light of these and other concerns, iPS cells may perhaps prove to be most useful in their potential to expand our overall understanding of stem cell biology, the net effect of which will provide the best hope of discovering new therapies for patients.

Many who oppose embryonic stem cell research believe for religious or other personal reasons that all preimplantation embryos have a moral standing equal to living persons. On the other hand, those who support embryonic stem cell research point out that not all religious traditions grant full moral standing to early-stage human embryos.

According to Jewish, Islamic, Hindu, and Buddhist traditions, as well as many Western Christian views, moral standing arrives much later during the gestation process, with some views maintaining that the fetus must first reach a stage of viability where it would be capable of living outside the womb. Living in a pluralistic society such as ours, supporters argue, means having to tolerate differences in religious and personal convictions over such theoretical matters as when, during development, moral standing first appears.

Other critics of embryonic stem cell research believe that all preimplantation embryos have the potential to become full-fledged human beings and that they should never have this potential destroyed. In response, stem cell supporters argue that it is simply false that all early-stage embryos have the potential for complete human life many fertility clinic embryos are of poor quality and therefore not capable of producing a pregnancy (although they may yield stem cells). Similarly, as many as 75% to 80% of all embryos created through intercourse fail to implant. Furthermore, no embryos have the potential for full human life until they are implanted in a womans uterus, and until this essential step is taken an embryos potential exists only in the most abstract and hypothetical sense.

Despite the controversies, embryonic stem cell research continues to proceed rapidly around the world, with strong public funding in many countries. In the U.S., federal money for embryonic stem cell research is available only for stem cell lines that are on the National Institutes of Health stem cell registry. However, no federal funds may be used to derive human embryonic stem cell lines; NIH funds may only be used to study embryonic stem cells that were derived using other funding sources.

Despite the lack of full federal commitment to funding embryonic stem cell research in the U.S., there are wide-ranging national regulatory standards. The National Academy of Sciences established guidelines in 2005 for the conduct of human embryonic stem cell research. (See Resources.) According to these guidelines, all privately and publicly funded scientists working with embryonic stem cells should have their research proposals approved by local embryonic stem cell research oversight (ESCRO) committees. ESCRO committees are to include basic scientists, physicians, ethicists, legal experts, and community members to look at stem-cell-specific issues relating to the proposed research. These committees are also to work with local ethics review boards to ensure that the donors of embryos and other human materials are treated fairly and have given their voluntary informed consent to stem cell research teams. Although these guidelines are voluntarily, universities and other research centers have widely accepted them.

At the global level, in 2016 the International Society for Stem Cell Research (ISSCR) released a comprehensive set of professional guidelines for human stem cell research, spanning both bench and clinical stem cell research. (See Resources.) Unlike the NAS guidelines, the ISSCR guidelines go beyond American standards, adding, for example, the recommendation that stem cell lines be banked and freely distributed to researchers around the world to facilitate the fields progress on just and reasonable terms.The potential for over-commercialization and restrictive patenting practices is a major problem facing the stem cell field today, which may delay or reduce the broad public benefit of stem cell research. The promise of broad public benefit is one of thejustifying conditions for conducting stem cell research; without the real and substantial possibility for public benefit, stem cell research loses one of its most important moral foundations.

However, providing useful stem-cell-based therapies in the future is not a simple proposition, either. Developing a roadmap to bring stem cell research into the clinic will involve many complex steps, which the new ISSCR guidelines help address. They include:

These and other difficult issues must be sorted out if stem cell research in all its forms is to fulfill its promise.

STEM CELL GLOSSARY

Newer ethical issues in stem cell research go far beyond the embryo debate, since they encompass all stem cell types, not just human embryonic stem cells, and because they involve human subjects who, despite what one may think about the moral status of preimplantation embryos, are unequivocally moral persons. No other emerging issue better encapsulates the above concern than the growing phenomenon of stem cell tourism. At present, stem cell-based therapies are the clinical standard of care for only afew conditions, such as hematopoietic stem cell transplants for leukemia and epithelial stem cell-based treatments for burns and corneal disorders. Unfortunately, some unscrupulous clinicians around the world are exploiting patients hopes by purporting to provide for large sums of money effective stem cell therapies for many other conditions. These so-called stem cell clinics advance claims about their proffered stem cell therapies without credible scientific rationale, transparency, oversight, or patient protections.

The administration of unproven stem cell interventions outside of carefully regulated research protocols endangers patients and jeopardizes the legitimate progress of translational stem cell scientific research. Patients who travel for unproven stem cell therapies put themselves at risk of physical and financial harm.

The ISSCR guidelines are a good point for thinking about this important problem. The guidelines allow for exceptional circumstances in which clinicians might attempt medically innovative care in a very small number of seriously ill patients, subject to stringent oversight criteria. These criteria include: independent peer review of the proposed innovative procedure and its scientific rationale; institutional accountability; rigorous informed consent and close patient monitoring; transparency; timely adverse event reporting; and a commitment by clinician-scientists to move to a formal clinical trial in a timely manner after experience with at most a few patients. By juxtaposing some current stem cell clinics against the standards outlined in the ISSCR guidelines, one may easily identify some clinics shortcomings and call into question the legitimacy of their purported claims of providing innovative care to patients.

Moving beyond past debates about embryo status to issues concerning the uses of all varieties of stem cells, one can begin to focus the bioethical discourse on areas that have a much broader consensus base of shared values, such as patient and research subject protections and justice. Justice may also call on regulatory and oversight bodies to include a greater involvement of community and patient advocates in the oversight of research. Dealing with the bioethics of stem cell research demands that we wrestle with these and other tough questions.

Insoo Hyun, PhD, is an associate professor of bioethics at Case Western Reserve University.

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Stem Cells - The Hastings Center

Skin Stem Cells Comments Off on Stem Cells – The Hastings Center | December 8th, 2019

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New Delhi: A team of scientists in Bengaluru has claimed that it was able to stimulate skin cells to secrete naturally occurring antibiotics that can help treat superbugs or drug-resistant bacteria.

Antibiotic drugs used to treat infections are increasingly becoming ineffective globally, with bacteria having developed resistance to them over time.

According to the latest study published last monthin journal Cell Reports, scientists have discovered a way to stimulate skin cells to secrete antimicrobial peptides (AMPs).

AMPs target and kill bacteria in such variable ways that few bacteria ever become resistant to these molecules. This makes them uniquely suited to treating antibiotic-resistant bacteria, also called superbugs.

So far, artificially creating effective AMPs for use as antibiotic had not been possible.The new discovery has the potential to treat and prevent infections for post-surgery wounds, especially in diabetic patients and those with weakened immune systems, the researchers said in a statement Thursday.

The team comprises scientists from the National Centre for Biological Sciences, an affiliate of the Tata Institute of Fundamental Research, the Institute for Stem Cell Science and Regenerative Medicine (inStem) and the R&D department of Unilever, all based in Bengaluru.

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To develop new strategies to deal with antimicrobial resistance, scientists from inStem and Unilever probed the cellular mechanisms that regulate the release of AMPs.

Apart from their role as natural antibiotics, AMPs are also known to be involved in wound healing.

Amitabha Majumdar, a researcher at Unilever, hypothesised that the same machinery used to release AMPs during wound-healing could be harnessed to control AMP release from skin cells for treating or preventing infections.

To test this, Majumdar worked with Colin Jamora, a researcher at inStems Centre for Inflammation and Tissue Homeostasis, whose group works extensively on the mechanisms of wound-healing in skin.

The team found a new signalling pathway for long-term release of AMPs from skin cells. Usually, AMPs are released to fight off bacterial infections when direct contact between skin epidermal cells and bacteria occurs. This process is triggered by a reduction in the levels of a protein called caspase-8.

The scientists found that using molecular techniques to reduce caspase-8 is enough to trigger the release of stored AMP from skin cells.

Their study showed that just by modulating caspase-8 levels in the skin, AMP release can be controlled to prevent a whole spectrum of infections.

This may be especially useful for diabetics and patients with weakened immune systems who are highly susceptible to bacterial, yeast, fungal, and viral infections in post-surgery wounds.

Over the last century, bacteria have evolved so much to protect themselves against antibiotics that the World Health Organisation (WHO) fears humankind may soon slip back into a situation similar to the pre-antibiotic era.

According to a WHO report, the death toll caused by antimicrobial resistance is estimated to rise to 10 million annually by 2050 with India carrying one of the largest burdens of drug-resistant pathogens worldwide.

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Antibiotic in human skin can beat superbugs. Now scientists have a way to put it to use - ThePrint

Skin Stem Cells Comments Off on Antibiotic in human skin can beat superbugs. Now scientists have a way to put it to use – ThePrint | December 8th, 2019