NEW YORK, Dec. 16, 2020 (GLOBE NEWSWIRE) -- Y-mAbs Therapeutics, Inc. (the “Company” or “Y-mAbs”) (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, today announced that data for DANYELZA® (naxitamab-gqgk), omburtamab and nivatrotamab will be presented at the Company’s R&D event, which takes place virtually today at 12 p.m. Eastern Time. Key opinion leaders, including Shakeel Modak, M.D., MRCP, Memorial Sloan Kettering (“MSK”), Jaume Mora, M.D., Ph.D., SJD Barcelona Children's Hospital, and Brian H. Santich, Ph.D., MSK, will discuss the current treatment landscape and unmet medical needs for high-risk neuroblastoma, osteosarcoma and other solid tumors. Investors, analysts, members of the media and public may access the event via a live webcast.

Read more:
Y-mAbs Announces Pipeline Update

Original post:
BioSyent Launches Combogesic®, First-Ever Acetaminophen + Ibuprofen Combination Tablet in Canada Now Available

An Emerging Markets News Commentary An Emerging Markets News Commentary

Visit link:
Emerging Markets Report: Doctor’s Orders

Read more here:
Tauriga Sciences Inc. Obtains its FEDLINKS Badge as a Verified Federal Government Vendor

Excerpt from:
AB Science will host a live webcast on December 17, 2020 on masitinib results in Alzheimer’s Disease

DURHAM, N.C., Dec. 16, 2020 (GLOBE NEWSWIRE) -- CoImmune, Inc. today announced that its CAR-CIK technology was featured at the annual American Society of Hematology (ASH) meeting with an interim update on the phase 1/2 dose escalation clinical trial in B-cell acute lymphoblastic leukemia (B-ALL). The trial is being conducted at Ospedale San Gerardo, Monza, Italy by principal investigator Andrea Biondi, M.D. and at Papa Giovanni XXIII, Bergamo, Italy by principal investigator Alessandro Rambaldi, M.D. The presentation on was on December 7th during the immunotherapy session and was given by Dr. Chiara Magnani of the Tettamanti Research Center, Monza, Italy.

See the original post here:
Chimeric antigen receptor (CAR)-modified cytokine induced killer cell (CAR-CIK) technology featured at ASH

Continue reading here:
Tauriga Sciences Inc. to Resume the Clinical Development of its Proposed “Anti-Nausea” Pharmaceutical Grade Version of Tauri-Gum

COPENHAGEN, Denmark, December 16, 2020 – Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) announced today that the U.S. Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services, has exercised an option covering the majority of the second year of performance under the USD $200 million order for JYNNEOS® (Smallpox and Monkeypox Vaccine, Live, Non-replicating) awarded in April 2020.

Visit link:
Bavarian Nordic Secures Second Part of Smallpox Vaccine Order from the U.S. Government

PHOENIX, Dec. 16, 2020 /PRNewswire/ --Creative Medical Technology Holdings Inc., (OTC CELZ) announced today positive preclinical data supporting the utilization of its ImmCelz cell based immunotherapy for treatment of stroke. In an animal model of ischemia stroke, the middle cerebral artery ligation model, administration of ImmCelz resulted in 34% reduction in infarct volume, whereas control bone marrow mesenchymal stem cells reduced infarct volume by 21%. Additionally, improvements in functional recovery where observed using the Rotarod test. At 28 days after induction of stroke the animals receiving ImmCelz had superior running time (92% of non-stroke controls) compared to animals which received bone marrow mesenchymal stem cells (73% of non-stroke control). Animals that received saline had a running time that was 50% of non-stroke controls.

"The regenerative potential of immune cells that have been programmed by stem cells is a fascinating and novel area of research." Said Dr. Amit Patel, coinventor of ImmCelz, and board member of the Company. "Conceptual advantages of using reprogrammed T cells include higher migratory ability due to smaller size, as well as ability to replicate and potentially form "regenerative memory cells."

"This data, which is covered by our previous filed patents, such as no. 15/987739, Generation of autologous immune modulatory cells for treatment of neurological conditions, demonstrate that immune modulation via this stem cell based method may be a novel and superior way of addressing the $30 billion dollar market for stroke therapeutics1." Said Dr. Thomas Ichim, coinventor of the patent and Chief Scientific Officer of the Company. "The fact that this technology, which has priority back to 2017, is demonstrating such stunning results, motivates us to consider filing an Investigational New Drug Application for use in stroke."

Creative Medical Technology Holdings possesses numerous issued patents in the area of cellular therapy including patent no. 10,842,815 covering use of T regulatory cells for spinal disc regeneration, patent no. 9,598,673 covering stem cell therapy for disc regeneration, patent no. 10,792,310 covering regeneration of ovaries using endothelial progenitor cells and mesenchymal stem cells, patent no. 8,372,797 covering use of stem cells for erectile dysfunction, and patent no. 7,569,385 licensed from the University of California covering a novel stem cell type.

"While stroke historically has been a major area of unmet medical need, the rise in stroke cases , as well as the fact that younger people are increasingly falling victim to stroke, strongly motivates us to accelerate our developmental programs and to continue to explore participation of Big Pharma in this space." Said Timothy Warbington, President and CEO of the Company. "We are eager to replicate the existing experiments start compiling the dossier needed to take ImmCelz into humans using the Investigational New Drug Application (IND) route through the FDA."

About Creative Medical Technology Holdings

Creative Medical Technology Holdings, Inc. is a commercial stage biotechnology company specializing in stem cell technology in the fields of urology, neurology and orthopedics and trades on the OTC under the ticker symbol CELZ. For further information about the company, please visitwww.creativemedicaltechnology.com.

Forward Looking Statements

OTC Markets has not reviewed and does not accept responsibility for the adequacy or accuracy of this release. This news release may contain forward-looking statements including but not limited to comments regarding the timing and content of upcoming clinical trials and laboratory results, marketing efforts, funding, etc. Forward-looking statements address future events and conditions and, therefore, involve inherent risks and uncertainties. Actual results may differ materially from those currently anticipated in such statements. See the periodic and other reports filed by Creative Medical Technology Holdings, Inc. with the Securities and Exchange Commission and available on the Commission's website atwww.sec.gov.

Timothy Warbington, CEO[emailprotected] CreativeMedicalHealth.com

Creativemedicaltechnology.comwww.StemSpine.comwww.Caverstem.comwww.Femcelz.com

1 Stroke Management Market Size Forecasts 2026 | Statistics Report (gminsights.com)

SOURCE Creative Medical Technology Holdings, Inc.

Home

Excerpt from:
Creative Medical Technology Holdings Announces Successful Application of ImmCelz Immunotherapy for Treatment of Stroke - PRNewswire

Autologous hematopoietic stem cell transplant (AHSCT) induces a reduction in relapse rate and physical disability in patients with relapsing-remitting multiple sclerosis (RRMS) who respond inadequately to other treatments, a small study suggests.

The study, Selective cognitive dysfunction and physical disability improvement after autologous hematopoietic stem cell transplantation in highly active multiple sclerosis, was published in the journal Nature Scientific Reports.

AHSCT is an experimental approach to treat multiple sclerosis (MS) that is meant to rebuild a patients immune system in order to stop attacks on the brain and spinal cord.

The procedure begins with collecting a patients own (meaning autologous) healthy hematopoietic stem cells immature cells that can develop into all types of blood cells from the bone marrow. These cells are put back into the patient after a fairly non-aggressive combination of chemotherapy is given to kill the patients immune cells.

A team of researchers at the Vilnius University, in Lithuania, evaluated the effectiveness and safety of the AHSCT procedure in 24 patients (18 female, mean age 37.8 years) with highly active RRMS (mean disease duration of 8.6 years) who failed to respond to conventional therapies.

The aim of the study was to assess cognitive dysfunction and physical disability after AHSCT, to explore the potential factors influencing disability regression after the transplant, and to estimate the safety of low-dose immunosuppressive therapy in highly active relapsing MS patients.

Researchers assessed participants disability and cognition through changes in several functional measures, including the expanded disability status scale (EDSS) and the Brief International Cognitive Assessment for MS, which includes three cognitive domains measured by the symbol digit modalities test, brief visuospatial memory test revised, and California verbal learning test second edition.

Of the 24 patients, 13 (54.2%) completed a 24-month follow-up and were included in the efficacy analysis of AHSCT. From those, two (15.4%) had one relapse during the first year after AHSCT and three patients (23.1%) had one relapse during the second year after AHSCT.

The annualized relapse rate (ARR) was 2.7 one year before AHSCT and 1.9 at two years before AHSCT. After the AHSCT procedure, ARR dropped to 0.2 in the first year and to 0.3 in the second year. This represented an 89% reduction in ARR, when comparing the values at two years after AHSCT with those at two years before AHSCT.

The researchers also noted a reduction in disability progression (as measured by EDSS scores), with 84.6% of patients improving their disability score after AHSCT at month six and 76.9% at one year. Additionally, 76.9% of patients showed stable disability scores two years after the transplant.

The findings of EDSS improvement in almost 85% of the patients suggest that disability may be often at least temporarily reversible in patients with highly active [relapsing] MS if they receive suitable and well-timed treatment, the researchers wrote.

Using appropriate statistical models, researchers found that the clinical variable that explained the disability regression at months 6 and 12 after AHSCT was the disability progression over 6 months before AHSCT.

Improvements in cognition after AHSCT also were observed. Specifically, the scores of information processing speed and verbal learning, measured by the symbol digit modalities test, were significantly higher at month 12 after AHSCT (56.8) when compared to month three (48.3).

The score of brief visuospatial memory test revised that assesses visuospatial memory was slightly lower at month three (25.6) than before AHSCT (27.8), however, the difference was not significant.

The score of the California verbal learning test, which assesses verbal learning, was significantly higher at month 12 (63.6) than before AHSCT (55.2).

No new or active lesions were found on MRI after AHSCT, suggesting that all patients remained without radiological disease activity.

Furthermore, regarding safety, the incidence and severity of adverse events (side effects) after AHSCT were in the expected range and all were resolved. There were no transplant-related deaths reported.

Researchers noted several limitations to the studys findings, including the low sample size and the fact that the patientss assessment and follow-ups were provided at the same center without a comparative group.

Nonetheless, the outcomes are highly promising, as compared to conventional MS treatment, the researchers wrote. Further research is needed to replicate these findings and to assess long-term outcomes and safety of AHSCT.

Diana holds a PhD in Biomedical Sciences, with specialization in genetics, from Universidade Nova de Lisboa, Portugal. Her work has been focused on enzyme function, human genetics and drug metabolism.

Total Posts: 1,053

Patrcia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

Follow this link:
Stem Cell Transplant Reduces Relapses and Disability in RRMS... - Multiple Sclerosis News Today

Cancer researchers have created a new class of drugs to selectively target and destroy myeloid leukaemia cells with TET gene mutations.

Photomicrograph of bone marrow biopsy showing myeloblasts of acute myeloid leukemia (AML), a cancer of white blood cells.

Researchers have developed a novel class of targeted cancer drug that may be highly effective for the treatment of myeloid leukaemias. According to the team, their synthetic molecule, called TETi76, was able to selectively kill cells with TET2 gene mutations, one of the most common driver mutations in myeloid leukaemias.

Myeloid leukaemias are cancers derived from stem and progenitor cells in the bone marrow that give rise to all normal blood cells. These malignancies are normally treated with chemotherapy, either alone or in combination with targeted drugs; however, the significant side-effects associated with this treatment mean a more selective/targeted treatment is desirable.

In a new study published inBlood Cancer Discovery, researchers from the Cleveland Clinics Taussig Cancer Institute and Lerner Research Institute, both US, describe a new pharmacological strategy to preferentially target and eliminate leukaemia cells with TET2 mutations.

In preclinical models, we found that a synthetic molecule called TETi76 was able to target and kill the mutant cancer cells both in the early phases of disease what we call clonal haematopoiesis of indeterminate potential, or CHIP and in fully developed TET2 mutant myeloid leukaemia, said Dr Jaroslaw Maciejewski, a practicing haematologist and chair of the Cleveland Clinic Department of Translational Hematology & Oncology Research, who has been investigating the TET2 gene for the last decade.

TET genes encode DNA dioxygenase enzymes, which remove chemical groups from DNA molecules. Their activity ultimately changes what genes are expressed and can contribute to the development and spread of disease.

TET genes act as tumour suppressors, so loss-of-function mutations are common in haematological cancers, like leukaemias. While all members of the TET family are dioxygenases, TET2 is the most powerful. Genetic TET2 deficiency has been shown to skew differentiation of blood cells and clonal expansion of progenitor and stem cells. However, its related genes TET1 and TET3 provide residual enzymatic activity, sufficient to facilitate the survival of these progenitor cells harbouring cancerous mutations, thereby promoting the spread of the cancer, even when TET2 is inactive.

In their study, the research team designed TETi76 to replicate and amplify the effects of a natural molecule called 2-hydroxyglutarate (2HG), which inhibits the enzymatic activity of TET genes. They hoped to selectively eliminate TET2 mutant leukaemia cells centres by targeting their reliance on this residual DNA dioxygenase activity.

We took lessons from the natural biological capabilities of 2HG, explained Dr Babal Kant Jha, Maciejewskis collaborator from the Department of Translational Hematology & Oncology Research. We studied the molecule and rationally designed a novel small molecule, synthesised by our chemistry group headed by Dr James Phillips. Together, we generated TETi76 a similar, but more potent version capable of inhibiting not just TET2, but also the remaining disease-driving enzymatic activity of TET1 and TET3.

The researchers studied TETi76s effects in both preclinical disease and xenograft models (where human cancer cells are implanted into preclinical models). In both models, treatment with the novel TET inhibitor suppressed the clonal evolution of TET2 mutant cells.

While the team cautioned that additional studies would be critical to investigate the small molecules cancer-fighting capabilities in patients, Dr Jha said we are optimistic about our results, which show not just that TETi76 preferentially restricts the growth and spread of cells with TET2 mutations, but also gives survival advantage to normal stem and progenitor cells.

Read more here:
Novel class of targeted cancer therapies could treat myeloid leukaemias - Drug Target Review

Victoria Gray (second from left) with children Jamarius Wash, Jadasia Wash and Jaden Wash. Now that the gene-editing treatment has eased Gray's pain, she has been able be more active in her kids' lives and looks forward to the future. "This is really a life-changer for me," she says. Victoria Gray hide caption

Victoria Gray (second from left) with children Jamarius Wash, Jadasia Wash and Jaden Wash. Now that the gene-editing treatment has eased Gray's pain, she has been able be more active in her kids' lives and looks forward to the future. "This is really a life-changer for me," she says.

The last thing a lot of people want to do these days is get on a plane. But even a pandemic would not stop Victoria Gray. She jumped at the chance to head to the airport this summer.

"It was one of those things I was waiting to get a chance to do," says Gray.

She had never flown before because she was born with sickle cell disease. She feared the altitude change might trigger one of the worst complications of the devastating genetic disease a sudden attack of excruciating pain.

But Gray is the first person in the United States to be successfully treated for a genetic disorder with the help of CRISPR, a revolutionary gene-editing technique that makes it much easier to make very precise changes in DNA.

About a year after getting the treatment, it was working so well that Gray felt comfortable flying for the first time. She went to Washington, D.C., to visit her husband, who has been away for months on deployment with the National Guard.

"It was exciting. I had a window. And I got to look out the window and see the clouds and everything," says Gray, 35, of Forest, Miss.

Gray wore a mask the whole time to protect herself against the coronavirus, kept her distance from other people at the airport, and arrived happily in Washington, D.C., even though she's afraid of heights.

"I didn't hyperventilate like I thought I would," Gray says, laughing as she recounts the adventure in an interview with NPR.

NPR has had exclusive access to follow Gray through her experience since she underwent the landmark treatment on July 2, 2019. Since the last time NPR checked in with Gray in June, she has continued to improve. Researchers have become increasingly confident that the approach is safe, working for her and will continue to work. Moreover, they are becoming far more encouraged that her case is far from a fluke.

At a recent meeting of the American Society for Hematology, researchers reported the latest results from the first 10 patients treated via the technique in a research study, including Gray, two other sickle cell patients and seven patients with a related blood disorder, beta thalassemia. The patients now have been followed for between three and 18 months.

All the patients appear to have responded well. The only side effects have been from the intense chemotherapy they've had to undergo before getting the billions of edited cells infused into their bodies.

The New England Journal of Medicine published online this month the first peer-reviewed research paper from the study, focusing on Gray and the first beta thalassemia patient who was treated.

"I'm very excited to see these results," says Jennifer Doudna of the University of California, Berkeley, who shared the Nobel Prize this year for her role in the development of CRISPR. "Patients appear to be cured of their disease, which is simply remarkable."

Another nine patients have also been treated, according to CRISPR Therapeutics in Cambridge, Mass., and Vertex Pharmaceuticals in Boston, two companies sponsoring the research. Those individuals haven't been followed long enough to report any results, officials say.

But the results from the first 10 patients "represent an important scientific and medical milestone," says Dr. David Altshuler, Vertex's chief scientific officer.

The treatment boosted levels of a protein in the study subjects' blood known as fetal hemoglobin. The scientists believe that protein is compensating for defective adult hemoglobin that their bodies produce because of a genetic defect they were born with. Hemoglobin is necessary for red blood cells to carry oxygen.

Analyses of samples of bone marrow cells from Gray six months after getting the treatment, then again six months later, showed the gene-edited cells had persisted the full year a promising indication that the approach has permanently altered her DNA and could last a lifetime.

"This gives us great confidence that this can be a one-time therapy that can be a cure for life," says Samarth Kulkarni, the CEO of CRISPR Therapeutics.

Gray and the two other sickle cell patients haven't had any complications from their disease since getting the treatment, including any pain attacks or hospitalizations. Gray has also been able to wean off the powerful pain medications she'd needed most of her life.

Prior to the treatment, Gray experienced an average of seven such episodes every year. Similarly, the beta thalassemia patients haven't needed the regular blood transfusions that had been required to keep them alive.

"It is a big deal because we we able to prove that we can edit human cells and we can infuse them safely into patients and it totally changed their life," says Dr. Haydar Frangoul at the Sarah Cannon Research Institute in Nashville. Frangoul is Gray's doctor and is helping run the study.

For the treatment, doctors remove stem cells from the patients' bone marrow and use CRISPR to edit a gene in the cells, activating the production of fetal hemoglobin. That protein is produced by fetuses in the womb but usually shuts off shortly after birth.

The patients then undergo a grueling round of chemotherapy to destroy most of their bone marrow to make room for the gene-edited cells, billions of which are then infused into their bodies.

"It is opening the door for us to show that this therapy can not only be used in sickle cell and thalassemia but potentially can be used in other disorders," Frangoul says.

Doctors have already started trying to use CRISPR to treat cancer and to restore vision to people blinded by a genetic disease. They hope to try it for many other diseases as well, including heart disease and AIDS.

The researchers stress that they will have to follow Gray and many other patients for a lot longer to be sure the treatment is safe and that it keeps working. But they are optimistic it will.

Gray hopes so too.

"It's amazing," she says. "It's better than I could have imagined. I feel like I can do what I want now."

The last year hasn't always been easy for Gray, though. Like millions of other Americans, she has been sheltering at home with three of her children, worrying about keeping them safe and helping them learn from home much of the time.

"I'm trying to do the things I need to do while watch them at the same time to make sure they're doing the things they need to do," Gray says. "It's been a tough task."

But she has been able do other things she never got to do before, such as watch her oldest son's football games and see her daughter cheerleading.

"This is really a life-changer for me," she says. "It's magnificent."

She's now looking forward to going back to school herself, learning to swim, traveling more when the pandemic finally ends, and watching her children grow up without them worrying about their mother dying.

"I want to see them graduate high school and be able to take them to move into dorms in college. And I want to be there for their weddings just everything that the normal people get to do in life. I want to be able to do those things with my kids," she says. "I can look forward now to having grandkids one day being a grandmama."

Excerpt from:
1st Patients To Get CRISPR Gene-Editing Treatment Continue To Thrive - NPR

Bone Regeneration Material Market: Introduction

Bone-regeneration techniques, either with autografts or allografts, represent a challenge for reconstructive surgery. Biomaterials are temporary matrices for bone growth and provide a specific environment and architecture for tissue development. Depending on the specific intended application of the matrix, whether for structural support, drug-delivery capability, or both, certain material categories may be more or less well suited to the final structure.

Read Report Overview - https://www.transparencymarketresearch.com/bone-regeneration-material-market.html

Key Drivers and Restraints of Global Bone Regeneration Material Market

Increase in prevalence of degenerative joint diseases boost the market. Worldwide estimates of degenerative joint diseases indicate that 9.6% men and 18.0% women above 60 years have symptomatic osteoarthritis. According to expert opinions presented in the EULAR committee report, radiographic evidence of knee osteoarthritis in men and women over 65 years of age is found in 30% of the population.

In the absence of disease modifying therapy, a large number of patients with osteoarthritis progress to advance joint destruction. Surgery with bone grafts and substitutes play a major role in the management of osteoarthritis to avoid advanced joint destruction. According to the American College of Rheumatology, advances in biomaterial and tissue engineering are expected to create new opportunities to integrate surgical approaches in osteoarthritis.

Request Brochure of Report - https://www.transparencymarketresearch.com/sample/sample.php?flag=B&rep_id=80488

Increase in the number of orthopedic surgeries also fuels the market. According to the American Academy of Orthopaedic Surgeons (AAOS), approximately 129,000 total knee arthroplasty (TKA) surgeries were performed in the U.S. in 1990, and the number has increased to over 600,000 in 2010. The AAOS has projected that 3 million TKA procedures would be performed by 2030 in the U.S. alone. Moreover, spinal surgeries are becoming increasingly popular, and approximately 432,000 spinal fusions are performed in the U.S. each year. Bone grafts and substitutes are extensively used for the surgeries mentioned above. This is likely to fuel the bone regeneration material market.

Bone graft and substitutes are a long-term solution to bone problem treatment; however, these are expensive. No two patients or their customized bone grafts and substitutes treatments are exactly alike. Hence, the number of appointments, procedures, and costs vary accordingly. Surgeons charge US$ 35,000 to US$ 40,000 for a complex posterolateral lumbar spine fusion bone graft surgery. Most surgeons refer patients to specialty surgeons, neurologists, or orthopedic physicians, which increases the cost of procedure. Asia is price-sensitive and displays inhibitions with respect to investing in bone graft and substitutes, which are often only affordable to the elite population; therefore offering a comparatively smaller market.

Request for Analysis of COVID-19 Impact on Bone Regeneration Material Market - https://www.transparencymarketresearch.com/sample/sample.php?flag=covid19&rep_id=80488

Cell-based Segment to Expand Significantly

Based on product type, the global bone regeneration material market can be divided into ceramic-based, polymer-based, growth factor-based, cell-based and others

The ceramic-based segment dominated the global market in 2019. It is projected to sustain its position during the forecast period. Ceramic-based bone grafts are widely used to reduce the need for iliac crest bone grafting. Rise in geriatric population with oral health issues across the world has augmented the number of bone graft surgeries performed in the last few years.

However, the cell based segment is projected to expand at a notable CAGR during the forecast period. Bone tissue engineering (BTE) using bone marrow stem cells has been suggested as a promising technique for reconstructing bone defect in order to overcome the drawbacks of bone graft materials.

Orthopedic surgery segment to dominate global bone regeneration material market

Based on application, the global bone regeneration material market can be segregated into orthopedic surgery, bone trauma, dental surgery and others.

In terms of revenue, the orthopedic surgery segment accounted for a prominent share of the market in 2019 owing to a rise in the geriatric population and increase in cases of orthopedic diseases. According to WHO, between 2015 and 2050, the proportion of the world's population over 60 years would nearly double from 12% to 22%. The number of people aged 60 years and older is estimated to outnumber children younger than 5 years by 2020. As per MVZ Gelenk-Klinik data, more than 2400 orthopedic surgical procedures are performed per year at the Gelenk Klinik Orthopaedic Hospital.

Request for Custom Research - https://www.transparencymarketresearch.com/sample/sample.php?flag=CR&rep_id=80488

North America to dominate global bone regeneration material market

In terms of region, the global bone regeneration material market can be divided into: North America, Europe, Asia Pacific, Latin America, and Middle East & Africa

North America accounted for a significant share of the bone regeneration material market in 2019, followed by Europe. Usage of new and innovative products in both premium and value segments among various bone grafts substitutes is projected to boost the bone regeneration material market in several countries in Europe and North America in the next few years. According to the Centers for Disease Control and Prevention (CDC), the total number of inpatient surgeries carried out in the U.S. were 51.4 million in 2014; of these 719,000 were total knee replacements and 332,000 were total hip replacement.

The market in developing countries in Asia Pacific is estimated to expand at a significant CAGR during the forecast period. The market in Asia Pacific is driven by an increase in population and time taken to accept new technologies. Increase in the number of patients and geriatric population are major factors that are expected to propel the market in Japan during the forecast period. According to the Gerontological Society of America, Japan has the highest proportion of geriatric population in the world. Hence, demand for orthopedic surgeries is estimated to be higher in Japan than that in other countries in Asia Pacific.

Pre Book Bone Regeneration Material Market Report at https://www.transparencymarketresearch.com/checkout.php?rep_id=80488&ltype=S

Key Manufacturers Operating in Market

The global bone regeneration material market was highly fragmented in 2019. Key manufacturers operating in the global market are:

Browse More Trending Reports by Transparency Market Research:

Tactile Imaging Market: https://www.transparencymarketresearch.com/tactile-imaging-market.html

Eye Stent Market: https://www.transparencymarketresearch.com/eye-stent-market.html

Podiatry Workstations Market: https://www.transparencymarketresearch.com/podiatry-workstations-market.html

About Us

Transparency Market Research is a next-generation market intelligence provider, offering fact-based solutions to business leaders, consultants, and strategy professionals.

Our reports are single-point solutions for businesses to grow, evolve, and mature. Our real-time data collection methods along with ability to track more than one million high growth niche products are aligned with your aims. The detailed and proprietary statistical models used by our analysts offer insights for making right decision in the shortest span of time. For organizations that require specific but comprehensive information we offer customized solutions through ad hoc reports. These requests are delivered with the perfect combination of right sense of fact-oriented problem solving methodologies and leveraging existing data repositories.

TMR believes that unison of solutions for clients-specific problems with right methodology of research is the key to help enterprises reach right decision.

ContactMr. Rohit BhiseyTransparency Market ResearchState Tower,90 State Street,Suite 700,Albany NY - 12207United StatesUSA - Canada Toll Free: 866-552-3453Email: sales@transparencymarketresearch.comWebsite: https://www.transparencymarketresearch.com/

Read more:
Bone Regeneration Material Market: Cell-based Segment to Expand Significantly - BioSpace

Over two million babies, children, and adults in the United States are living with congenital heart disease--a range of birth defects affecting the heart's structure or function. Now, researchers at Gladstone Institutes and UC San Francisco (UCSF) have made inroads into understanding how a broad network of genes and proteins go awry in a subset of congenital heart diseases.

"We now have a better understanding of what genes are improperly deployed in some cases of congenital heart disease," says Benoit Bruneau, PhD, director of the Gladstone Institute of Cardiovascular Disease and a senior author of the new study. "Eventually, this might help us get a handle on how to modulate genetic networks to prevent or treat the disease."

Congenital heart disease encompasses a wide variety of heart defects, ranging from mild structural problems that cause no symptoms to severe malformations that disrupt or block the normal flow of blood through the heart. A handful of genetic mutations have been implicated in contributing to congenital heart disease; the first to be identified was in a gene known as TBX5. The TBX5 protein is a transcription factor--it controls the expression of dozens of others genes, giving it far-reaching effects.

Bruneau has spent the last 20 years studying the effect of TBX5 mutations on developing heart cells, mostly conducting research in mice. In the new study published inDevelopmental Cell, he and his colleagues turned instead to human cells, using novel approaches to follow what happens in individual cells when TBX5 is mutated.

"This is really the first time we've been able to study this genetic mutation in a human context," says Bruneau, who is also a professor in the Department of Pediatrics at UCSF. "The mouse heart is a good proxy for the human heart, but it's not exactly the same, so it's important to be able to carry out these experiments in human cells."

The scientists began with human induced pluripotent stem cells (iPS cells), which have been reprogrammed to an embryonic-like state, giving them--like embryonic stem cells--the ability to become nearly every cell type in the body.

Then, Bruneau's group used CRISPR-Cas9 gene-editing technology to mutate TBX5 in the cells and began coaxing the iPS cells to become heart cells. As the cells became more like heart cells, the researchers used a method called single-cell RNA sequencing to track how the TBX5 mutation changed which genes were switched on and off in tens of thousands of individual cells.

The experiment revealed many genes that were expressed at higher or lower levels in cells with mutated TBX5. Importantly, not all cells responded to the TBX5 mutation in the same way; some had drastic changes in gene expression while other were less affected. This diversity, the researchers say, reflects the fact that the heart is composed of many different cell types.

"It makes sense that some are more affected than others, but this is the first experimental data in human cells to show that diversity," says Bruneau.

Bruneau's team then collaborated with computational researchers to analyze how the impacted genes and proteins were related to each other. The new data let them sketch out a complex and interconnected network of molecules that work together during heart development.

"We've not only provided a list of genes that are implicated in congenital heart disease, but we've offered context in terms of how those genes are connected," says Irfan Kathiriya, MD, PhD, a pediatric cardiac anesthesiologist at UCSF Benioff Children's Hospital, an associate professor in the Department of Anesthesia and Perioperative Care at UCSF, a visiting scientist at Gladstone, and the first author of the study.

Several genes fell into known pathways already associated with heart development or congenital heart disease. Some genes were among those directly regulated by TBX5's function as a transcription factor, while others were affected in a less direct way, the study revealed. In addition, many of the altered genes were relevant to heart function in patients with congenital heart disease as they control the rhythm and relaxation of the heart, and defects in these genes are often found together with the structural defects.

The new paper doesn't point toward any individual drug target that can reverse a congenital heart disease after birth, but a better understanding of the network involved in healthy heart formation, as well as congenital heart disease may lead to ways to prevent the defects, the researchers say. In the same way that folate taken by pregnant women is known to help prevent neural tube defects, there may be a compound that can help ensure that the network of genes and proteins related to congenital heart disease stays balanced during embryonic development.

"Our new data reveal that the genes are really all part of one network--complex but singular--which needs to stay balanced during heart development," says Bruneau. "That means if we can figure out a balancing factor that keeps this network functioning, we might be able to help prevent congenital heart defects."

Reference: Kathiriya IS, Rao KS, Iacono G, et al. Modeling Human TBX5 Haploinsufficiency Predicts Regulatory Networks for Congenital Heart Disease. Developmental Cell. 2020. doi:10.1016/j.devcel.2020.11.020.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

Continue reading here:
Network of Genes Involved in Congenital Heart Disease Identified - Technology Networks

The agreement will accelerate the development and availability of new medical and pharmaceutical therapies to improve patients lives

Hamamatsu Photonics UK Ltd and Medical Technologies Innovation Facility (MTIF) are pleased to announce they have entered into a partnership agreement enabling customers the ability to view and utilize Hamamatsus Functional Drug Screening System (FDSS) CELL. This is the first FDSS/CELL to be made available in the UK in this way.

This new collaboration aims to leverage the photonics expertise, novel proprietary technology and applications of Hamamatsu, with the significant medical technology research and development capabilities of MTIF.

This is a high-end specialist piece of equipment utilised in the development of innovative medicines around the world. We are very excited to be able to provide customers with this capability, that complements our own research using this technically superb equipment. Says Professor John Hunt, Head of Strategic Research at MTIF and within Nottingham Trent University.

This partnership provides companies with a unique opportunity to use cutting edge high through-put technology to screen compounds for pharmacological activity. These capabilities are usually unavailable to all but the largest organisations. This collaboration allows organisations of every size the opportunity to accelerate their drug discovery programme. Says Professor Mike Hannay, Managing Director of the Medical Technologies Innovation Facility (MTIF) .

Hamamatsu has a long history in developing cutting edge scientific equipment for the life science market; our FDSS/CELL enables scientists, such as those working at MTIF, to make breakthroughs in the field of drug discovery and compound research. We are really excited about this new partnership between Hamamatsu and the team at MTIF helping to make such advanced instrumentation available to hundreds of potential users throughout the UK research community. Tim Stokes, Managing Director of Hamamatsu Photonics UK Ltd.

The FDSS/CELL is a compact, easy to use screening system that enables monitoring of GPCRs and ion channels for drug discovery and life science research. Screening various compounds at high throughput (96 / 384 well assays) is enabled by fluorescence or luminescence measurements using a highly sensitive Hamamatsu camera, which captures cell dynamics under the same conditions with no time lag between wells. It is also capable of recording changes in electrical potential in iPSC-derived neuronal and cardiac stem cells to gain a better understanding of toxic compound effects.

Through this new technical collaboration, HPUK and MTIF will organically integrate their respective advanced technologies and development capabilities to showcase this novel laboratory screening technology onsite at MTIF in Nottingham, UK.

Hamamatsu Photonics and MTIF aim to benefit the UK life science sector by accelerating the availability of new medical and pharmaceutical therapies. By aligning capabilities and ambitions, the parties will deliver benefit to clients by helping them to successfully navigate the complexities of discovering drug and cell therapy candidates.

Want the latest science news straight to your inbox? Become a SelectScience member today >>

See the original post:
Industry News: Hamamatsu Photonics UK Ltd and the Medical Technologies Innovation Facility enter into a partnership agreement - SelectScience

If youre like 95% of American adults, you had chickenpox as a kid. Before the United States started its widespread vaccination program in 1995, there were roughly four million cases of chickenpox every year. So, most people suffered through an infection with this highly contagious virus and its itchy, whole-body rash.

But unlike many childhood viruses, the varicella-zoster virus that causes chickenpox doesnt clear from the body when the illness ends. Instead it hangs around, taking up residence and lying dormant in the nerves, sometimes for decades, with the immune system holding it in check. In some people, it lives there harmlessly for the rest of their life. But in others, the virus can suddenly emerge and strike again, this time appearing as a different condition known as shingles.

Like chickenpox, shingles also causes a blistering rash, but this time it generally appears as a painful band around one side of your ribcage or on one side of your face. The first symptom for many people is pain or a burning sensation in the affected area. You may also have fever, a headache, and fatigue. Along with the rash and other temporary symptoms, shingles can also bring unpleasant, long-lasting, and sometimes permanent complications, such as skin infections, nerve pain in the area where the rash appeared, or even vision loss.

Experts dont fully understand this. One theory is that shingles occurs when your immune system loses its ability to keep the virus in check.

After you get chickenpox, your immune system is able to recognize the varicella-zoster virus thanks to specialized immune system cells, called B and T cells, that are able to remember the virus and quickly marshal an attack on it. Factors that weaken the immune system increase your risk of developing shingles. These include

While you may not be able to control certain factors that might trigger shingles, there are strategies you can use to prevent shingles. The most important is vaccination. Research shows that the shingles vaccine Shingrix is 90% effective in preventing an outbreak of shingles. Even if you do get shingles after being vaccinated, Shingrix greatly reduces your risk of developing persistent pain in the affected area, known as post-herpetic neuralgia.

In addition to getting vaccinated, its always a good idea to take steps to keep your body healthy, such as choosing healthy foods, staying active, and getting sufficient sleep. Its not clear if healthy lifestyle habits like these can prevent shingles, but even if they dont, theyre worthwhile because they will benefit your body in many other ways.

Read the rest here:
Shingles: What triggers this painful, burning rash? - Harvard Health Blog - Harvard Health

As interest in chimeric antigen receptor (CAR) T-cell therapy continues to grow with more promising data coming out and approvals from the FDA in various hematologic malignancies, the role of this cellular therapy has yet to be defined in multiple myeloma, but recent data have inspired hope for this therapy in the relapsed/refractory population.

The B-cell maturation antigen (BCMA)directed CAR T-cell therapy idecabtagene vicleucel (ide-cel; bb2121) has generated excitement in this population following the submission of a Biologics License Application (BLA) in March 2020, seeking approval of ide-cel in patients with multiple myeloma who have received at least 3 prior therapies, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody, and a Priority Review designation granted in September 2020. Following delays in the review due to coronavirus disease 2019, the Prescription Drug User Fee Act action date has been set as March 27, 2021.

Deep and durable responses were observed with ide-cel as treatment of heavily pretreated patients with relapsed/refractory multiple myeloma, according to updated results from the CRB-401 study presented by Yi Lin, MD, PhD, assistant professor of oncology and associate professor of medicine at Mayo Clinic, during the 2020 American Society of Hematology (ASH) Annual Meeting. The efficacy and safety findings were consistent with prior findings and supported a favorable clinical risk-benefit profile at target dose levels 150 x 106.1

The median overall survival with ide-cel was 34.2 months (95% CI, 19.2-not evaluable) among all patients in this triple-classexposed population, and half of the patients who had ongoing responses achieved a duration of response >2 years. The median progression-free survival (PFS) was 8.8 months (95% CI, 5.9-11.9). The objective response rate (ORR) overall was 75.8%, which included complete responses (CRs) in 38.7%.

These results from CRB-401 are comparable to the findings from the pivotal phase 2 KarMMa study (NCT03361748), which were presented earlier this year during the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program and support the Biologics License Application. The median OS for this study was 19.4 months, and the median PFS was 8.8 months. The ORR was 73%, which included a CR rate of 33%, and the median duration of response was 10.7 months.2

Ide-cel is being explored in several ongoing studies as well, including the phase 2 KarMMa-2 (NCT-3601078), phase 3 KarMMa-3 (NCT03651128), and phase 1 KarMMa-4 (NCT04196491) clinical trials. These phase 2 and 3 studies are evaluating ide-cel in patients with triple-classexposed disease, and the phase 1 study will explore the use of this CAR T-cell therapy in patients with high-risk newly diagnosed multiple myeloma.

These data have also set the stage for other BCMA-directed CAR T-cell therapies in development for the treatment of patients with multiple myeloma.

In an interview with Targeted Oncology, Lin discussed the updated findings from the CRB-401 study of ide-cel as treatment of patients with relapsed/refractory multiple myeloma.

TARGETED ONCOLOGY: What historical data have we seen with BCMA-directed CAR T-cell therapy in patients with relapsed/refractory multiple myeloma?

Lin: With the CAR T approach in multiple myeloma, the very first case report was actually with CD19-targeted CAR T because there was already experience with that particular antigen in leukemia and lymphomas. There's some ongoing effort in terms of dual targeting with CD19 and BCMA, but BCMA very quickly emerged as an ideal candidate for the myeloma space. This is an antigen that is more uniformly expressed on plasma cells, including myeloma cells, and maybe a small subset of mature B cells, but otherwise BCMA is not expressed on healthy tissues.

There have been some single-center clinical trials with the BCMA-targeted CAR T approach prior to the CRB-401 study, both with National Cancer Institute and the University of Pennsylvania with slightly different constructs. With those early phase 1 studies, there was a little bit more toxicity seen, although there was certainly some response, but the response wasn't particularly durable. CRB-401 is the first in a series of now industry-sponsored multicenter studies, in which we are now seeing a much more encouraging durable response rate and also a more favorable side effect profile as well. At ASH this year, I presented the longer follow-up on the phase 1 CRB-401 study. There is a pivotal phase 2 KarMMa study using the same CAR T construct that had been presented at ASCO earlier this year.

TARGETED ONCOLOGY: Please describe the design of the trial and what was different about the study.

Lin: The CRB-401 study has 2 parts. The first part is the dose-escalation part, and the second part is the dose expansion. The dose escalation is basically testing the range of a fixed dose of 50 million all the way up to 800 million of ide-cel CAR T cells in a relatively small number of patients, basically looking for signs of severe side effects to identify a safe dose. The dose expansion cohort is where we take the more promising doses in terms of response, and also safety profile, and test them in more patients to get a better safety signal, which is then moved forward for phase 2 testing in the KarMMa study.

In the dose-expansion portion of CRB-401, we required that each patient must have had exposure to an anti-CD38 antibody. That was allowed in a dose escalation but not required for everybody. [To be included in the study,] the patient must have had become refractory to the most recent line of treatment before they came on the study. The other thing that was different was that in the dose-escalation cohort, all patients had their myeloma cells in the bone marrow reviewed centrally by immunohistochemistry staining, and they were required to have at least 50% of these cells having BCMA expression in a dose-expansion cohort, to better understand the clinical efficacy and safety profiles of this treatment. We also included some patients that had BCMA expression below that to even levels that were not detectable by immunohistochemistry.

TARGETED ONCOLOGY: What were the results from this study?

Lin: The study [included] a total of 62 patients. The results from the first 33 patients were already published in the New England Journal of Medicine last year, and this year at ASH, data were presented for outcomes of the entire 62-patient cohort, with a median follow-up of now 18.1 months. What we have seen so far is in this entire treated patient cohort these are patients with very high-risk features of myeloma, and close to a third of these patients had high-risk cytogenetics, 37% of these patients had extra modularity plasma effect, and almost half of these patients needed some type of systemic therapy while their CAR T cells are being made. These patients, on average, had 6 lines of prior therapy, and in close to 70% or higher, these patients are either triple-refractory or were refractory to the most recent line of therapy.

For this group of patients that was treated overall, the safety signal was very tolerable, which is not surprising with CAR T therapy because these patients also do get lymphodepletion chemotherapy as part of the treatment with CAR T. We do see that low blood count is the most common side effect, including the more severe low blood counts, but on average, the recovery of these blood counts can be seen well under the first 3 months after CAR T infusion. The other most common side effects that we need to watch for with CAR T are cytokine release syndrome (CRS) and neurotoxicity. What we have seen in this study is that, on average, about 76% of these patients had some type of CRS. However, those that had grade 3 or higher, that is only [seen] in 6.5% of the patients, so much lower, and that's also reflected in the relative lower use of tocilizumab and steroids, as well, to manage the side effects. About 35% of these patients had some type of neurologic side effect, but again, only 1 patient had a more severe form of neurotoxicity. Compared to what we have seen with the CAR T experience in the lymphoma/leukemia space, this is a very, very encouraging safety profile.

We have also now seen that the ORR is quite high. It's 75.8% with a CR and stringent CR rate of about 38.7%. Many of these patients that had bone marrow that were evaluable for minimal residual disease (MRD) response were MRD-negative. We are seeing, since we tested many doses, that there is a dose-related increase in response with increasing [the] dose, and we have also seen that the duration of response is 10.3 months. When we look at the dose that was tested as well in those expansions [in] the 150 to 450 range, what we have seen is that the duration of response is comparable, so not significantly decreased, for patients with high-risk features like those with extramedullary disease for older patients, as well as patients who needed to get bridging therapy during treatment. The median PFS is 8.8 months, and the median OS is 34.2 months.

So far, the response rate, duration of response, and PFS seem to be comparable to what we also now see in the KarMMa study, which has less follow-up, but we are seeing a very nice median OS for a treatment in which we're just giving a 1 dose infusion and no follow-up maintenance therapy.

TARGETED ONCOLOGY: In terms of CAR T-cell therapy, how do you see this strategy impacting this patient population in the future?

Lin: I think there's definitely a role for this in the practice. The BLA for ide-cel has been submitted to the FDA, so we're anticipating review sometime in early 2021. This is very exciting because this could very well be the first CAR T for multiple myeloma. I think this would definitely be a treatment option for these patients. Based on how KarMMa is designed, we anticipate that the FDA approval will be in the space of patients who [have] had at least 3 lines of prior therapy and have been exposed to the currently approved 3 main backbones of treatmenta PI, IMiD, and the CD38 antibody. The full detail is pending final FDA review and the label. However, in that space, certainly looking at the demographic of the patient that's been treated so far as CRB-401 and KarMMa, that's a wider group of patients. Based on the fact that this is a treatment that is a basically living active cells, I perceive that the earlier that patient could get this therapy in the earliest possible approved indication, there would likely be potentially more benefit for the patients.

TARGETED ONCOLOGY: Do you think there is hope for this treatment in other hematologic malignancies outside of lymphomas and leukemias as well?

Lin: That is actually a very interesting question because what we're seeing in terms of the severity of CRS and neurotoxicity is a reflection of our evolving learning about how to manage the toxicity, as well. There is a component to the CAR design, the disease, the nature of the disease, the kinetics of the CAR T actions, in the manifestation of these symptoms. What we are seeing now, with even the prior CAR and next-generation CAR coming on, we will likely see an ongoing improvement in terms of a reduction of severity of these symptoms and also in the ways that we could manage these symptoms.

The fact that myeloma would be the next disease that has an FDA-approved CAR T also relates to the fact that the BCMA antigen is more restricted on the cell type where the malignancy is involved, similar to CD19 for lymphoid malignancy. We are seeing that there are some challenges, for example with acute myeloid leukemia or myeloid neoplasms where a number of antigens could overlap with stem cells, which we wouldn't want to try to hurt. There are some novel CAR approaches to try to overcome that, and those are in very early phase testing, so we'll need to see how those results evolve.

References

1. Lin Y, Raje NS, Berdeja JG, et al. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in patients with relapsed and refractory multiple myeloma: updated results from phase 1 CRB-401 study. Presented at: 2020 ASH Annual Meeting & Exposition; December 5-8, 2020; Virtual. Abstract 131.

2. Munshi NC, Anderson Jr LD, Jagannath S, et al. Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results.J Clin Oncol. 2020;38(suppl):8503. doi:10.1200/JCO.2020.38.15_suppl.8503

See the rest here:
Updated Findings Show Continued Efficacy for CAR T-Cell Therapy in Heavily Pretreated Myeloma - Targeted Oncology

The allogeneic off-the-shelf CD22-directed T-cell product, UCART22, showed early signs of activity and no evidence of unexpected toxicities at 2 dose levels for adult patients with relapsed/refractory CD22-positive B-cell acute lymphoblastic leukemia, according to the results of a study presented during the 2020 ASH Annual Meeting.1

In the phase 1 BALLI-01 (NCT04150497) dose-escalation and dose-expansion study, 2 patients at the 1 x 105 cells/kg dose achieved a complete remission (CR) with incomplete hematologic recovery on day 28. One of these patients attained a minimal residual disease (MRD)positive CR at day 42 followed by subsequent inotuzumab ozogamicin (Besponsa) and then transplant.

One patient at dose level 2, 1 x 106 cells/kg, experienced a significant bone marrow blast reduction at day 28, followed by disease progression.

No patients experienced dose-limiting toxicities (DLTs), immune effector cellassociated neurotoxicity syndrome (ICANS), graft-versus-host disease (GVHD), adverse effects (AE) of special interest (AESI), a UCART22-related AE that was grade 3 or higher, or a serious AE (SAE).

UCART22 showed no unexpected toxicities at the doses of 1 x 105 cells/kg and 1 x 106 cells/kg with fludarabine and cyclophosphamide lymphodepletion, lead study author Nitin Jain, MD, an assistant professor in the Department of Leukemia, The University of Texas MD Anderson Cancer Center, said in a virtual presentation during the meeting. Host immune recovery was observed early, and the addition of alemtuzumab [Lemtrada] to fludarabine and cyclophosphamide lymphodepletion is currently being explored with the goal to achieve deeper and more sustained T-cell depletion and to promote expansion and persistence of UCART22.

Standard treatment for adult patients with B-cell ALL includes multiagent chemotherapy with or without allogeneic stem cell transplant. However, 30% to 60% of patients with newly diagnosed B-cell ALL who achieve a CR will relapse, and the expected 5-year survival rate for those with relapsed/refractory disease is approximately 10%.

Previously, UCART19, when paired with lymphodepletion using fludarabine, cyclophosphamide, and alemtuzumab, was found to show efficacy in this patient population.2

CD22 is an FDA-approved therapeutic target in B-cell ALL. UCART22 is an immediately available, standardized, manufactured agent with the ability to re-dose, and its CAR expression redirects T cells to tumor antigens, Jain explained.

Moreover, through its mechanism of action, TRAC becomes disrupted using Transcription activator-like effector nucleases (Talen) technology to eliminate TCR from cell surface and reduce the risk of GVHD. CD52 is also disrupted with the use of Talen to eliminate sensitivity to lymphodepletion with alemtuzumab. Finally, there is a CD20 mimotope for rituximab (Rituxan) as a safety switch, Jain added.

UCART22 has also demonstrated in vivo antitumor activity in immune-compromised mice that were engrafted with CD22-positive Burkitt lymphoma cells in a dose-dependent manner.

In the dose-escalation/dose-expansion BALLI-01 study, investigators are enrolling up to 30 patients in a modified Toxicity Probability Interval design. There are 3 cohorts, which have 2 to 4 patients on each cohort: 1 x 105 cells/kg (dose level 1), 1 x 106 cells/kg (dose level 2), and 5 x 106 cells/kg. The focus of the dose-escalation phase of the trial was to determine the maximum-tolerated dose (MTD) and the recommended phase 2 dose (RP2D) before heading into the dose-expansion portion of the trial.

To be eligible for enrollment, patients must have been between 18 and 70 years old, have acceptable organ function, an ECOG performance status of 0 or 1, at least 90% of B-cell ALL blast CD22 expression, and had previously received at least 1 standard chemotherapy regimen and at least 1 salvage regimen.

End points of the trial included safety and tolerability, MTD/R2PD, investigator-assessed response, immune reconstitution, and UCART22 expansion and persistence.

The lymphodepletion regimens were comprised of fludarabine (at 30 mg/m2 x 4 days) plus cyclophosphamide (1 g/m2 x 3 days); the study has since been amended to include the regimen of fludarabine (at 30 mg/m2 x 3 days), cyclophosphamide (500 g/m2 x 3 days), and alemtuzumab (20 mg/day x 3 days) and is currently enrolling patients.

Following screening, lymphodepletion, and UCART22 infusion, patients underwent an observation period for DLTs with a primary disease evaluation at 28 days; additional efficacy evaluations occurred at 56 days and 84 days. Patients were followed for 2 years and continued to be assessed for long-term follow-up.

As of July 1, 2020, 7 patients were screened, of which 1 patient failed and 6 were therefore enrolled on the study. One patient discontinued therapy before receiving UCART22 due to hypoxia from pneumonitis that was linked with lymphodepletion. Five patients were treated with UCART22 at dose level 1 (n = 3) and dose level 2 (n = 2).

The median age of participants was 24 years (range, 22-52), 3 of the 5 patients were male, and 3 had an ECOG performance status of 0. The median number of prior therapies was 3 (range, 2-6), and there were a median 35% bone marrow blasts (range, 10%-78%) prior to lymphodepletion.

Three patients had complex karyotype and 2 had diploid cytogenetics. One patient each had the following molecular abnormalities: CRLF2, CRLF2 and JAK2, CDKN2A loss, KRAS and PTPN11, and IKZF1. Only 1 patient had undergone haploidentical transplant. Four patients previously received prior CD19- or CD22-directed therapy, including blinatumomab (Blincyto), inotuzumab ozogamicin (Besponsa), and CD19-directed CAR T-cell therapy. At study entry, 3 patients had refractory disease and 2 patients had relapsed disease.

Grade 3 or higher treatment-emergent AEs (TEAEs), which were unrelated to study treatment, included hypokalemia, anemia, increased bilirubin, and acute hypoxic respiratory failure. Also not related to UCART22, 3 patients experienced 4 treatment-emergent SAEs: porta-hepatis hematoma, sepsis, bleeding, and sepsis in the context of disease progression. No treatment discontinuations due to a treatment-related TEAE were reported.

The patient who achieved a CR followed by transplant was a 22-year-old male who had undergone 2 prior treatments for B-cell ALL and received UCART22 at a dose of 1 x 105 cells/kg. He did not experience CRS, ICANS, GVHD, nor a SAE, and all TEAEs were grade 1.

Jain also noted that host T-cell constitution was observed in all patients within the DLT observation period. UCART22 was also not detectable through flow cytometry or molecular analysis, the latter of which was at dose level 1 only.

References:

1. Jain N, Roboz GJ, Konopleva M, et al. Preliminary results of BALLI-O1: a phase I study of UCART22 (allogeneic engineered T cells expressing anti-CD22 chimeric antigen receptor) in adult patients with relapsed/refractory anti-CD22+ B-cell acute lymphoblastic leukemia (NCT04150497). Presented at: 2020 ASH Annual Meeting and Exposition; December 4-8, 2020; Virtual. Abstract 163.

2. Benjamin R, Graham C, Yallop D, et al. Preliminary data on safety, cellular kinetics and anti-leukemic activity of UCART19, an allogeneic anti-CD19 CAR T-cell product, in a pool of adult and pediatric patients with high-risk CD19+ relapsed/refractory b-cell acute lymphoblastic leukemia. Blood. 2018;132(suppl 1):896. doi:10.1182/blood-2018-99-111356.

Excerpt from:
Early Signs of Activity and Tolerability Found in Allogeneic Product UCART22 for Patients with Relapsed/Refractory CD22+ B-Cell ALL - Cancer Network

The Covid-19 can damage the heart both directly and indirectly, and lead to complications ranging from inflammation of the heart (myocarditis), injury to heart cells (necrosis), heart rhythm disorders (arrhythmias), heart attack, and muscle dysfunction that can lead to acute or protracted heart failure, experts said.

Covid-19 is a vascular disease that injures heart cells and muscle. It also leads to the formation of blood clots, both in the microvasculature and large vessels, which can block blood supply to the heart, brain and lungs and lead to stroke, heart attack and respiratory failure, said Dr Ravi R Kasliwal, chairman of clinical and preventive cardiology department at Medanta -The Medicity Hospital.

Also Read: Few Covid-19 deaths in Indias old-age homes, survey finds

A US study using MRI found cardiac abnormalities in 78 of 100 patients who had recently recovered from Covid-19, including 12 of 18 asymptomatic patients. Sixty patients had ongoing myocardial inflammation consistent with myocarditis, found the study, which was published in the Journal of American Medical Association Cardiology in July.

Even people with mild disease or no symptoms can develop life-threatening cardiovascular complications. Whats worrying is that this holds true for healthy adults with no pre-existing risk factors, which raise their risk of complications, said Dr Kasliwal, who recommends that everyone who has recovered from Covid-19 be screened for heart damage

Cardiac trouble

Extensive cardiac involvement is what differentiates Sars-CoV-2, the virus that causes Covid-19, from the six other coronaviruses that cause infection in humans, writes cardiologist Dr Eric J Topol, founder, director and professor of molecular medicine at the Scripps Research Translational Institute in La Jolla, California, in the journal Science.

The four human coronaviruses that cause cold-like symptoms have not been associated with heart abnormalities, though there have been isolated reports linking the Middle East Respiratory Syndrome (MERS) caused by MERS-CoV) with myocarditis, and cardiac disease with the Severe Acute Respiratory Syndrome (SARS) caused by Sars-CoV.

Also Read| Extraordinary uncertainties: Harvard prof on Covid-19, impact on mental health

Sars-CoV-2 is structurally different from Sars-CoV. The virus targets the angiotensin-converting enzyme 2 (Ace2) receptor throughout the body, facilitating cell entry by way of its spike protein, along with the cooperation of proteases. The heart is one of the many organs with high expression of Ace2. The affinity of Sars-CoV-2 to Ace2 is significantly greater than that of SARS, according to Dr Topol.

Topol notes the ease with which Sars-CoV-2 infects heart cells derived from induced pluripotent stem cells (iPSCs) in vitro, leading to a distinctive pattern of heart muscle cell fragmentation evident in autopsy reports. Besides directly infecting heart muscle cells, Sars-CoV-2 also enters and infects the endothelial cells that line the blood vessels to the heart and multiple vascular beds, leading to a secondary immune response. This causes blood pressure dysregulation, and activation of a proinflammatory response leading to a cytokine storm, which is a potentially fatal systemic inflammatory syndrome associated with Covid-19.

Persisting problems

Studies have found that injury to heart cells reflected in blood concentrations of a cardiac muscle-specific enzyme called troponin affects at least one in five hospitalised patients and more than half of those with pre-existing heart conditions, which raises the risk of death. Patients with higher troponin amounts also have high markers of inflammation (including C-reactive protein, interleukin-6, ferritin, lactate dehydrogenase), high neutrophil count, and heart dysfunction, all of which heighten immune response.

The heightened systemic inflammatory responses and diminished blood supply because of clotting, endotheliitis (blood vessel inflammation), sepsis, or hypoxemia (oxygen deprivation) because of acute lung infection leads to indirect cardiac damage, said Dr Kasliwal.

The cardiovascular damage associated with Sars-CoV-2 infection can persist beyond recovery. Since the virus affects the heart as much as the respiratory tract, further research is needed to understand why some people are more vulnerable to heart damage than others.

View original post here:
Covid-19 can have impact on heart too, say experts - Hindustan Times

WALTHAM, Mass., Dec. 14, 2020 (GLOBE NEWSWIRE) -- AMAG Pharmaceuticals, Inc. has submitted its response to the FDA’s Notice of Opportunity for a Hearing (“NOOH”) regarding the Agency’s proposal to withdraw approval for Makena—also referred to as 17-OHPC—the only FDA-approved treatment, along with five generic versions, to reduce preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth.

Read more:
AMAG Pharmaceuticals Files Submission in Response To the Food And Drug Administration’s Notice of Opportunity for a Hearing and Proposal To Withdraw...