Stem Cell Clinic

Hematologist/Stem Cell Biologist to Direct Hematology and Cellular Therapy at Cedars-Sinai – Newswise

Newswise LOS ANGELES (Dec. 1, 2020) -- Internationally recognized hematologist John P. Chute, MD, has been selected to direct the Division of Hematology and Cellular Therapy in the Department of Medicine at Cedars-Sinai Cancer. The physician-scientist also will serve as director of the Center for Myelodysplastic Diseases Research and associate director of the Board of Governors Regenerative Medicine Institute in the Department of Biomedical Sciences. Chute assumed his new post Nov. 23.

The selection of Chute, following a national search, reflects the importance of his pioneering research in blood-forming stem cells called hematopoietic stem cells, which can self-renew and generate all cell types found in the blood and immune system. Over the past decade, Chute's lab has discovered several growth factors produced by the cells that line the walls of blood vessels; they play a critical role in blood-forming stem cell regeneration.

"Dr. Chute is an exceptional addition to our faculty," saidDanTheodorescu, MD, PhD, director ofCedars-Sinai Cancer. "His international reputation as a physician-scientist who has made major contributions to stem cell and hematopoietic cell biologywill greatly contribute to positioning the newly created Division of Hematology and Cell Therapy as one of the best in the nation, while providing Cedars-Sinai Cancer patients with exciting new options for the treatment of blood malignancies."

In addition to his hematopoietic stem cell research, Chute said he looks forward to expanding Cedars-Sinai's CAR T-cell research and therapy. He describes the immune-boosting therapeutic as "transformative" for patients with advanced non-Hodgkinlymphoma,childhood acute lymphoblastic leukemiaand potentially several additional blood cancers.

CAR T-cell therapy is a type of immunotherapy in which patients' own immune cells, called T cells, are collected from their blood, and then an artificial receptor chimeric antigen receptor, or CAR is added to the cells' surface. The receptor enables the modified cells to specifically eradicate cancer cells. The cells are infused back into a patient's body intravenously, where they multiply and attack tumor cells.

"CAR T therapy has become an important treatment option for so many patients with advanced cancer who had no options before," Chute said. "That's what makes CAR T therapy so exciting."

Chute joins Cedars-Sinai from the David Geffen School of Medicine at the UCLA, where he was a professor of Medicine and Radiation Oncology in the Division of Hematology/Oncology and an investigator in the Broad Stem Cell Research Center.

Chute earned his medical degree at Georgetown University. He completed his residency in internal medicine and fellowship in Hematology/Oncology at the National Naval Medical Center. He completed his research training at the National Cancer Institute and the Naval Medical Research Institute.

"I'm excited to join the Cedars-Sinai Cancer faculty because of the opportunity to collaborate with the world-class scientists and top-tier physicians at the cancer center," Chute said. "Cedars-Sinai has always been a leading medical center and is deeply committed to basic and translational research, while also growing the hematology and cellular therapy specialties. I'm eager to play a leading role in that growth."

Clickhereto read more from the Cedars-Sinai Newsroom.

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Hematologist/Stem Cell Biologist to Direct Hematology and Cellular Therapy at Cedars-Sinai - Newswise

Boston Celtics Kemba Walker will miss time after stem cell injection in left knee, will be re-evaluated in J – MassLive.com

Boston Celtics guard Kemba Walker will miss time at the start of the season after receiving a stem-cell injection in his left knee, the team announced Tuesday morning.

Per the Celtics, Walker consulted with multiple specialists before settling on a treatment in early October. His timeline for a return was 12 weeks, and he will be re-evaluated in early January. The NBA season is scheduled to open on Dec. 22, so Walker will miss time and then could be limited afterward as the Celtics try to tend to his knee as best they can.

Walker struggled with knee issues all year, playing in just 56 of Bostons regular-season games. He appeared limited at times when the season resumed in the Disney World bubble as well, despite a four-month layoff.

Walker, who is 30, signed a four-year, $140 million contract with the Celtics in 2019.

Per the Celtics, second-year wing Romeo Langford will also miss time. He had a procedure to repair a torn scapholunate ligament in his right wrist in September and was expected to miss four-to-five months. Per the Celtics, his recovery is proceeding on schedule.

Tristan Thompson also suffered a minor hamstring strain and will for the first week of training camp.

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Boston Celtics Kemba Walker will miss time after stem cell injection in left knee, will be re-evaluated in J - MassLive.com

Stem cell therapy in coronavirus disease 2019: current evidence and future potential – DocWire News

This article was originally published here

Cytotherapy. 2020 Nov 9:S1465-3249(20)30932-4. doi: 10.1016/j.jcyt.2020.11.001. Online ahead of print.

ABSTRACT

The end of 2019 saw the beginning of the coronavirus disease 2019 (COVID-19) pandemic that soared in 2020, affecting 215 countries worldwide, with no signs of abating. In an effort to contain the spread of the disease and treat the infected, researchers are racing against several odds to find an effective solution. The unavailability of timely and affordable or definitive treatment has caused significant morbidity and mortality. Acute respiratory distress syndrome (ARDS) caused by an unregulated host inflammatory response toward the viral infection, followed by multi-organ dysfunction or failure, is one of the primary causes of death in severe cases of COVID-19 infection. Currently, empirical management of respiratory and hematological manifestations along with anti-viral agents is being used to treat the infection. The quest is on for both a vaccine and a more definitive management protocol to curtail the spread. Researchers and clinicians are also exploring the possibility of using cell therapy for severe cases of COVID-19 with ARDS. Mesenchymal stromal cells are known to have immunomodulatory properties and have previously been used to treat viral infections. This review explores the potential of mesenchymal stromal cells as cell therapy for ARDS.

PMID:33257213 | DOI:10.1016/j.jcyt.2020.11.001

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Stem cell therapy in coronavirus disease 2019: current evidence and future potential - DocWire News

Hematologist Discusses the Impact a Myeloma CAR T-Cell Approval Would Have on the Treatment Landscape – DocWire News

Ankit Kansagra, MD, an assistant professor in theDepartment of Internal Medicineat UT Southwestern Medical Center and assistant director of theOutpatient Stem Cell Transplant Program, discusses chimeric antigen receptor T-cell agents in the pipeline for multiple myeloma (MM) and how these therapies may impact the treatment landscape pending future approvals.

In part two of this interview with Dr. Kansagra, available December X, he discusses potential new combination therapy options for MM.

DocWire News: Dr. Kansagra, can you discuss some of the CAR T-cell therapies in development for multiple myeloma, including their targets, clinical trial data that weve seen, and your expectations for any future FDA approvals?

Dr. Kansagra: In multiple myeloma, a few of the CAR T-cell therapy targets, which in the most developments, have been the BCMA-targeted CAR T-cell therapies. Those have been most exciting because they have made it to the phase I to phase II trials, especially the registrational studies from Celgene or Bluebird, BMS, the bb2121 compound or the Janssen compound 4538, being farthest out in the clinical development for CAR T-cell therapy. There are certainly a few other CAR T-cell therapies for multiple myeloma, which have grown, and theyre probably in the earlier development of therapy. An example being the CD38 CAR T-cell therapy, the SLAMF CAR T-cell therapy, and GPR5CD CAR T-cell therapy. Those are the three different targets which are being evaluated as T-cell targets.

DocWire News: How do you see the approval of these CAR T-cell therapy impacting the treatment landscape for multiple myeloma?

Dr. Kansagra: I think its going to be a huge improvement in our momentum of our treatment options. We have already seen cell therapy in myeloma have impressive results in terms of the response rates. I think the first important step is you have these patients who have got six or seven different lines of treatment, and now they are getting a novel product or a novel mechanism of action and also novel target and seeing an impressive response rate. That was amazing. Thats step number one.

Step number two is, as we have got further into the clinical development of CAR T-cell therapy, we have seen the safety of these products because that is extremely important that our products are safer.

Then the third thing which we have seen is that long-term follow-ups are not there, but what we have started seeing is that our responses, which could last up to a year or a year and a half for the population, where we would have usually seen maybe barely a response in a matter of months.

I think those are exciting times for our patients with multiple myeloma, where they have failed a lot of therapies. I think the more exciting times are going to come when we will start seeing these CAR T-cell therapies, potentially even in earlier lines of treatment options, where they could use maybe as a second-line treatment or as a first-line treatment after stem cell transplant or in lieu of stem cell transplant, maybe we can have deeper and longer remission rates.

DocWire News: With some of these agents potentially coming to market, do you foresee any challenges, either associated with adverse events or the ability to make these treatments widely available to patients?

Dr. Kansagra: Access to care is certainly near and dear to me, and thinking about those challenges is extremely, extremely important. I think were going to probably face challenges in a lot of different ways.

The first thing is, obviously, how can we get our patients to the centers who are giving CAR T-cell therapy? How are we going to bring them? We know from our autologous stem cell transplant over the last three to four decades, that still not every eligible transplant patient is referred to a transplant center, for whatever reasons. There are multiple reasons; there are socioeconomic reasons; there are distance reasons. But a lot of them are fixable reasons. There are some which are unfixable, but there are some fixable. I think the first and the foremost important thing is going to be to get our patients to a place who is delivering CAR T-cell therapy. Thats the challenge number one.

Challenge number two is, once they are in there, making sure that they are able to get that thing. So it means theyre not coming too late in their game, so trying to make sure theyre referred in earlier points, so that processes in place, that insurance approval has got started, if we need to work on the sociodemographic issues, how are they going to stay in a particular area? What is the social help, what is the family help theyre going to need? If they had referred earlier on, thats another, I call it, bottleneck that we need to think of that. Thats where we need to act on it.

The hard thing is obviously the cost. We dont know what is going to be the cost of the myeloma CAR T-cell therapy, or what is the price of those things. We can certainly estimate that its not going to be as cheap given the three CAR-Ts, which are not FDA-approved. I think its going to be expensive. You will have to think of the cost of care model of how we are going to work with this.

Last but not least of the challenges are the CAR-T itself. These are in the logistical challenge bucket. Then there are the challenges in the CAR-T landscape or the product itself. We still know that these are second-generation CAR T-cell therapies. They dont work for everybody. They have a high response rates, but they dont last that long. We hope to see longer remissions. An example I give, in comparison to large-cell lymphoma, we had 50% of the people who plateaued out, now coming up to about three years. In myeloma, we havent obviously made it to three years since the CAR T-cell therapy have started, but we do worry that there is a tail end of the curve that people are already relapsing to it. Obviously, that goes to the product itself or the construct itself, which needs to be developed in multiple different ways. I think of them as two major challenges ahead of us.

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Hematologist Discusses the Impact a Myeloma CAR T-Cell Approval Would Have on the Treatment Landscape - DocWire News

Sphingosine 1-phosphate Receptor Modulator ONO-4641 Regulates Trafficking of T Lymphocytes and Hematopoietic Stem Cells and Alleviates Immune-Mediated…

This article was originally published here

J Pharmacol Exp Ther. 2020 Nov 30:JPET-AR-2020-000277. doi: 10.1124/jpet.120.000277. Online ahead of print.

ABSTRACT

ONO-4641 is a second-generation sphingosine 1-phosphate (S1P) receptor modulator that exhibits selectivity for S1P receptors 1 and 5. Treatment with ONO-4641 leads to a reduction in magnetic resonance imaging disease measures in patients with relapsing-remitting multiple sclerosis. The objective of this study was to explore the potential impact of ONO-4641 treatment based on its immunomodulatory effects. Severe aplastic anemia is a bone marrow (BM) failure disease, typically caused by aberrant immune destruction of blood progenitors. Although the T helper type-1-mediated pathology is well described for aplastic anemia, the molecular mechanisms driving disease progression remain undefined. We evaluated the efficacy of ONO-4641 in a mouse model of aplastic anemia. ONO-4641 reduced the severity of BM failure in a dose-dependent manner, resulting in higher blood and BM cell counts. By evaluating the mode of action, we found that ONO-4641 inhibited the infiltration of donor-derived T lymphocytes to the BM. ONO-4641 also induced the accumulation of hematopoietic stem cells in the BM of mice. These observations indicate, for the first time, that S1P receptor modulators demonstrate efficacy in the mouse model of aplastic anemia and suggest that treatment with ONO-4641 might delay the progression of aplastic anemia. Significance Statement ONO-4641 is a second-generation sphingosine 1-phosphate (S1P) receptor modulator selective for S1P receptors 1 and 5. In this study, we demonstrated that ONO-4641 regulates the trafficking of T lymphocytes along with hematopoietic stem and progenitor cells leading to alleviation of pancytopenia and destruction of bone marrow in a bone marrow failure-induced mouse model mimicking human aplastic anemia.

PMID:33257316 | DOI:10.1124/jpet.120.000277

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Sphingosine 1-phosphate Receptor Modulator ONO-4641 Regulates Trafficking of T Lymphocytes and Hematopoietic Stem Cells and Alleviates Immune-Mediated...