Category Archives: Stem Cell Medical Center

Immunotherapy Inches Forward in Development of Myeloid Malignancies – OncLive

Survival for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains poor, and although immunotherapy has been positioned as a holy grail, it would be preemptive to predict its future based on the number of small studies that have been performed to date, according to Amer Zeidan, MD, MHS.

Nonetheless, one of the first studies that showed the potential for checkpoint inhibition in hematologic malignances was a phase 1/1b study that evaluated ipilimumab (Yervoy) after allogeneic stem cell transplant. In the study, ipilimumab was administered at a dose of 3 mg/kg and 10 mg/kg every 3 weeks. The results demonstrated efficacy in patients who received the 10 mg/kg dose. Specifically, 5 of 13 patients with heavily pretreated AML achieved a complete response (CR).

Ipilimumab has also demonstrated activity in patients with relapsed/refractory MDS in a single-arm study of 29 patients. Although the marrow CR rate was only 3.4%, 7 patients experienced prolonged stable disease for 46 weeks or more, including 3 patients with stable disease surpassing 1 year. Moreover, the median survival was 9.8 months (295 days; 95% CI, 240-671+).

In correlative analysis, we observed that patients who had increased expression of the costimulatory marker ICOS seemed to have better disease stabilization, so the direction is clearly headed toward trying to select patients using biomarker-driven strategies, Zeidan, an associate professor of medicine in the Department of Internal Medicine and Section of Hematology at Yale University School of Medicine, Yale Cancer Center, said in a presentation during the5th Annual International Congress on Immunotherapies in Cancer.

In another phase 2 study that evaluated the combination of nivolumab (Opdivo) and azacitidine vs ipilimumab and azacitidine in MDS, a higher response rate was observed with either combination compared with ipilimumab alone, at 70% and 62% vs 30%, respectively. However, the median overall survival (OS) was similar, at 11.8 months, not reached, and 8.5 months, respectively, said Zeiden.

Pembrolizumab (Keytruda) is also being subject to research in myeloid malignancies. Specifically, in a phase 1b study in combination with entinostat in MDS after failure on hypomethylating agents (HMAs). Data from the study have yet to read out, but are highly anticipated, said Zeiden.

Findings from a phase 2 study (NCT02775903) however stunted some of the excitement that had been generated with immunotherapy, putting into perspective the work that had been done to date. When the combination of a checkpoint inhibitor and an HMA, specifically durvalumab (Imfinzi) and azacitidine, was taken into a randomized trial vs azacitidine alone in patients with high-risk MDS and older AML, no difference was seen in progression-free survival (PFS) or OS.

Bispecific antibodies are another treatment class under investigation as a potential avenue forward for immunotherapy. One such antibody is sabatolimab, which targets IgG4 and TIM-3, and is the focus of several ongoing studies in MDS and AML. Specifically, the phase 2 STIMULUS-MDS1 (NCT03946670) and phase 3 STIMULUS-MDS2 (NCT04266301) trials in MDS and phase 2 STIMULUS-AML1 trial (NCT04150029) in AML.

Another path that will be explored is that of checkpoint inhibition plus chemotherapy, explained Zeiden. In a phase 2 study, the combination of pembrolizumab and 7+3 chemotherapy will be evaluated as frontline therapy in fit patients with AML.

The combination of azacitidine and venetoclax (Venclexta) has become the standard of care for older patients with AML, and preclinical evidence suggests that the BCL-2 inhibitor can augment the antitumor response of PD-L1 inhibitors.

As such, investigators have launched the phase 2 BLAST AML 2 study in which unfit patients with AML will be randomized to azacitidine plus venetoclax vs azacitidine/venetoclax plus pembrolizumab as frontline therapy.

Anti-CD47 antibodies are also under study and have shown promising, though early, activity in AML and MDS. For example, in combination with azacitidine, magrolimab has shown objective responses exceeding 60% in untreated AML and 90% in untreated MDS, with CR rates of 41% and 50%, respectively.

Importantly, a lot of the responses seem to occur in patients who have TP53 mutations, which is one of the highest areas of unmet need in AML and MDS, because those patients do very poorly with conventional treatment, said Zeidan.

Although magrolimab will move forward in development, Zeidan cautioned that the antitumor effects of anti-CD47 antibodies may not be class specific. For example, in a phase 1 study, CC-90002 failed to demonstrate any benefit in patients with relapsed/refractory AML and higher-risk MDS.

In conclusion, Zeidan stated, Many of the studies that have been conducted are single-arm trials with small sample sizes. [However,] we are doing more and more randomized studies using novel inhibitors against TIM-3 and CD47. The field is definitely exciting for us, and we are hoping to see some clinical activity for our patients soon.

Reference

Zeidan A. Immunotherapy for treatment of myeloid malignancies: will it fill the promise? Presented at: 5thAnnualInternational Congress on Immunotherapies in Cancer; December 12, 2020; virtual. gotoper.com/go/ICIC20Virtual

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Immunotherapy Inches Forward in Development of Myeloid Malignancies - OncLive

Cytovia Therapeutics Partners with National Cancer Institute to Develop Novel Gene-Edited, iPSC-Derived GPC3 CAR NK Cells for the Treatment of Solid…

January 13, 2021 07:47 ET | Source: Cytovia Therapeutics

CAMBRIDGE, Mass., Jan. 13, 2021 (GLOBE NEWSWIRE) -- Cytovia Therapeutics, an emerging biopharmaceutical company focusing on Natural Killer cells in cancer, announced today that it has signed a licensing agreement with the National Cancer Institute (NCI), part of the National Institutes of Health, to apply its gene-edited iPSC-derived NK cell technology to develop GPC3 CAR NK cell therapeutics. Dr Mitchell Ho, PhD, Director of the Antibody Engineering Program and Deputy Chief of the Laboratory of Molecular Biology at the NCI Center for Cancer Research has developed novel antibodies and chimeric antigen receptors (CAR) binding to glypican-3 (GPC3) on liver cancer cells. Dr. Ho has published data on the humanized GPC3 antibody in scientific reports (nature research) in 2016 as well as on the GPC3 CAR in Gastroenterology in 2020.

GPC3 is an oncofetal antigen involved in Wnt-dependent cell proliferation. It is highly expressed in Hepatocellular Carcinoma tumor cells as well as multiple other solid tumors, including ovarian cancer and lung cancer, but not expressed in adult normal tissues.

Cytovia has also signed a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute. Under the CRADA, Cytovia will collaborate with Dr. Hos laboratory to develop and evaluate gene-edited iPSC-derived GPC3 CAR NK cells. Cytovia expects to file an initial new drug application (IND) for its GPC3 CAR NK cells in the first half of 2022.

Dr. Daniel Teper, Chairman and CEO of Cytovia Therapeutics commented: GPC3 is an exciting new validated target for Hepatocellular Carcinoma, an area of major unmet medical need, as well as other solid tumors. We look forward to collaborating with Dr. Ho, a pioneer in GPC3 research, to develop a novel gene-edited, iPSC-derived GPC3 CAR NK that will advance toward a cure for liver cancer.

Dr. Ho added: Natural Killer cells play a major role in the immuno-surveillance of liver cancer. GPC3 is expressed in more than 70% of Hepatocellular Carcinoma cells but not on healthy cells. We look forward to investigating whether GPC3 CAR-NK therapy could provide a new safe and effective off-the-shelf option for patients with liver cancer.

ABOUT GENE-EDITED, IPSC-DERIVED NK CELLS Chimeric Antigen Receptors (CAR) are fusion proteins that combine an extracellular antigen recognition domain with an intracellular co-stimulatory signaling domain. Natural Killer (NK) cells are modified genetically to allow insertion of a CAR. CAR-NK cell therapy has demonstrated initial clinical relevance without the limitations of CAR-T, such as Cytokine Release Syndrome, neurotoxicity or Graft vs Host Disease (GVHD). In addition, CAR-NKs are naturally allogeneic, available off-the-shelf and may be able to be administered on an outpatient basis. Recent innovative developments with the induced pluripotent stem cell (iPSC)-derived CAR-NKs, an innovative technology, allow large quantities of homogeneous genetically modified CAR NK cells to be produced from a gene-edited iPSC master cell bank, and thus hold promise to expand access to cell therapy for many patients.

ABOUT HCC Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a leading cause of death worldwide, with 800,000 new cases diagnosed globally every year. The incidence in Asia is amongst the highest in the world (75%) with 400,000 in China alone. In the US, it is estimated to reach upwards of 30,000 by the end of 2020 and continues to be on the rise. Despite advances in immunotherapy, with current treatment options including multi-kinase inhibitors (TKI) and checkpoint inhibitors, life expectancy for patients diagnosed with HCC remains very low. The disease is often diagnosed at an advanced stage, with a median survival of approximately 6 to 20 months following diagnosis, and a 5-year survival rate below 10% in the US. Fortunately, new options including cell therapy and bispecific antibodies offer promise towards a cure for liver cancer.

ABOUT GPC3 Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan expressed in the liver and the kidney of fetuses but is hardly expressed in adults, except in the placenta. However, it is highly expressed in HCC, ovarian clear cell carcinoma, squamous cell carcinoma of the lung, melanoma, hepatoblastoma, nephroblastoma (Wilms tumor), yolk sac tumor, and some pediatric cancers. GPC3 promotes Wnt-dependent cell proliferation and has been strongly suggested that it is related to the malignant transformation. Therefore, GPC3 is a promising target for cancer immunotherapy and can serve as a biomarker for predicting tumor recurrence and treatment efficacy.

About Cytovia TherapeuticsCytovia Therapeutics Inc is an emerging biotechnology company that aims to accelerate patient access to transformational immunotherapies, addressing several of the most challenging unmet medical needs in cancer. Cytovia focuses on Natural Killer (NK) cell biology and is leveraging multiple advanced patented technologies, including an induced pluripotent stem cell (iPSC) platform for CAR (Chimeric Antigen Receptors) NK cell therapy, next-generation precision gene-editing to enhance targeting of NK cells, and NK engager multi-functional antibodies. Our initial product portfolio focuses on both hematological malignancies such as multiple myeloma and solid tumors including hepatocellular carcinoma and glioblastoma. The company partners with the University of California San Francisco (UCSF), the New York Stem Cell Foundation (NYSCF), the Hebrew University of Jerusalem, INSERM, and CytoImmune Therapeutics.

Learn more atwww.cytoviatx.comand follow Cytovia Therapeutics on Social Media(Facebook,LinkedIn,Twitter,and Youtube).

Contact for investor enquiries:

Anna Baran-Djokovic Vice President, Investor Relations Anna@cytoviatx.com 1 (646) 355 1787

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Cytovia Therapeutics Partners with National Cancer Institute to Develop Novel Gene-Edited, iPSC-Derived GPC3 CAR NK Cells for the Treatment of Solid...

Kaleido Biosciences Announces Positive Interim Results of Controlled Study of KB109 in Patients with Mild-to-Moderate COVID-19 – BioSpace

Preliminary analysis (n=176) demonstrates favorable safety and tolerability; data provide a strong signal of clinical benefit for subjects reporting one or more comorbidities

Topline data from full study population of 350 patients and results of second study of KB109 are expected in the first quarter of 2021

LEXINGTON, Mass., Jan. 14, 2021 (GLOBE NEWSWIRE) -- Kaleido Biosciences Inc. (Nasdaq: KLDO), today announced positive interim results from the K031 non-IND controlled clinical study evaluating outpatients with mild to moderate COVID-19 disease. Patients in this non-IND clinical study were randomized within 48 hours of testing positive for COVID-19 to either receive Supportive Self Care (SSC) or SSC plus Microbiome Metabolic Therapy (MMT) candidate KB109 for two weeks and then followed for an additional three weeks. The planned interim analysis comprised approximately half of the total study population (n=176) and showed that KB109 was well tolerated, with a safety profile consistent with previous studies of MMT candidates and no unexpected treatment-related adverse events. For subjects reporting one or more comorbidities, the median time to resolution of the thirteen overall COVID-19 related symptoms was 18 days with KB109 plus SSC and 27 days with SSC alone.

This interim analysis, from the largest study conducted to date with an MMT candidate, reinforces the safety and tolerability previously observed with MMTs and provides a strong signal of clinical benefit for KB109, commented Dan Menichella, President and Chief Executive Officer of Kaleido. The study reveals that many patients with mild-to-moderate disease, and particularly those patients with a comorbidity, experience symptoms for a period of weeks. This study shows the significant burden experienced by these patients and we look forward to reporting the full dataset later this quarter.

These exciting and relevant data are in line with what we are seeing in the COVID-19 literature and suggests that the microbiome plays a role in this disease, said John P.Haran, M.D., Ph.D., associate professor of emergency medicine, microbiology &physiological systems and clinical director of the UMass Center for Microbiome Research at the University of Massachusetts Medical School. There is increasing evidence supporting the biological plausibility that microbiome restoration has a significant impact on different diseases and seeing an influence in COVID-19 patients with comorbidities aligns with this emerging science.

Summary of Interim Results

The K031 study of 350 subjects is fully enrolled with results expected in the first quarter of 2021. Topline data from a smaller 50 subject study of KB109 is also expected in the first quarter of 2021.

About the Potential Role of the Microbiome in COVID-19

COVID-19 infection has been associated with activation of an inappropriate inflammatory cascade, which in some patients can cause an abnormally aggressive immune response that can lead to pneumonia and respiratory failure. Metabolites such as short chain fatty acids (SCFAs) produced by the microbiome through utilization of glycans are modulators of the immune response and therefore could play a role in limiting this inflammatory cascade.

In preclinical models, increased SFCAs and/or SFCA-producing taxa, have been shown to influence immune pathways, mitigate immune pathology, and improve survival and morbidity associated with severe respiratory viral infections.1,2 Commensal microbiota composition critically regulates the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection.3

In-human data also support the role of SCFAs in reducing the impact of viral infections.In patients undergoing hematopoietic stem cell transplants who have contracted respiratory viral infections, including coronavirus, the presence of SCFA-producing taxa has been associated with a significantly reduced risk of progression to lower respiratory tract infections, which can have substantial morbidity in this patient population.4 KB109 is Generally Recognized as Safe (GRAS) and was selected for evaluation in these COVID-19 clinical studies based on its demonstrated ability to increase production of SCFAs as well as to promote commensal bacteria and reduce pathogenic bacteria ex vivo.

About Microbiome Metabolic Therapies (MMT)

Kaleidos Microbiome Metabolic Therapies, or MMTs, are designed to drive the function and distribution of the microbiomes existing microbes in order to decrease or increase the production of metabolites, or to advantage or disadvantage certain bacteria in the microbiome community. The Companys initial MMT candidates are targeted, synthetic glycans that are orally administered, have limited systemic exposure, and are selectively metabolized by enzymes in the microbiome.Kaleido utilizes its discovery and development platform to study MMTs in microbiome samples to rapidly advance MMT candidates rapidly into clinical studies in healthy subjects and patients. These human clinical studies are conducted under regulations supporting research with food, evaluating safety, tolerability and potential markers of effect. For MMT candidates that are further developed as therapeutics, the Company conducts clinical trials under an Investigational New Drug (IND) or regulatory equivalent outside the U.S., and in Phase 2 or later development.

AboutKaleido Biosciences

Kaleido Biosciencesis a clinical-stage healthcare company with a differentiated, chemistry-driven approach to targeting the microbiome to treat disease and improve human health. The Company has built a proprietary product platform to enable the rapid and cost-efficient discovery and development of novel Microbiome Metabolic Therapies (MMT).MMTs are designed to modulate the metabolic output and profile of the microbiome by driving the function and distribution of the guts existing microbes. Kaleido is advancing a broad pipeline of MMT candidates with the potential to address a variety of diseases and conditions with significant unmet patient needs. To learn more, visithttps://kaleido.com/.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the therapeutic potential of our MMT candidates, the timing of initiation, completion and reporting of results of clinical studies, and our strategy, business plans and focus. The words may, will, could, would, should, expect, plan, anticipate, intend, believe, estimate, predict, project, potential, continue, target and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on managements current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those related to the breadth of our pipeline of product candidates, the strength of our proprietary product platform, the efficiency of our discovery and development approach, the fact that interim results from KB013 may not accurately predict final results from KB013 and that such final results may not support continued development of KB109, the clinical development and safety profile of our MMT candidates and their therapeutic potential, whether and when, if at all, our MMT candidates will receive approval from theU.S. Food and Drug Administration and for which, if any, indications, competition from other biotechnology companies, and other risks identified in ourSECfilings, including our most recent Form 10-Q, and subsequent filings with theSEC. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We disclaim any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements.

Contacts Kaleido Biosciences William Duke, Jr. Chief Financial Officer 617-890-5772 william.duke@kaleido.com

Investors Mike Biega Solebury Trout 617-221-9660 mbiega@soleburytrout.com

Media Rich Allan Solebury Trout 646-378-2958 rallan@soleburytrout.com

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Kaleido Biosciences Announces Positive Interim Results of Controlled Study of KB109 in Patients with Mild-to-Moderate COVID-19 - BioSpace

Doctors Make Medical Breakthrough In Treating Severe Cases Of COVID – CBS San Francisco

MIAMI (CBSMiami) Doctors in South Florida say an experimental treatment involving stem cells has been incredibly successful in treating severe cases of COVID.

The study involved patients at Jackson Memorial Hospital and at the University Miami Tower. Many of them had acute respiratory distress syndrome (ARDS).

I think this could be a turning point, said Dr. Camillo Ricordi, director of the Cell Transplant Center at the University of Miami Miller School of Medicine.

According to Ricordi, the groundbreaking treatment uses stem cells from a babys umbilical cord.

The treatment has shown to safely reduce the risk of death and has made recovery time faster for some of the most ill patients.

We just published the study that using stem cells derived from the umbilical cord of a healthy newborn baby. We generally throw away the placenta that is discarded after birth. But we are using cells that are extracted and expand from that umbilical cord. That can generate and provide therapeutic doses for over 10,000 patients from a single umbilical cord. It is an amazing result, he said.

Ricordi, one of the lead researchers of the study, said treating coronavirus patients with these mesenchymal stem cells just made sense.

When the COVID pandemic exploded, I called our collaborators in China, saying, Why dont we try to use these cells in COVID? Because they have the same properties that help us fight autoimmune conditions, he explained.

The FDA approved to go forward with the trial.

In a double blind study, involving 24 patients with acute respiratory distress syndrome, each received two infusions given days apart of either the stem cells or placebo.

The physician nor the patient knew if someone received a cell or just an infusion of the solution of the cells, Ricordi said.

Researchers found the patient survival rate treated with the stem cells was 91%.

Ricordi said these stem cells have potential to restore normal immune response and also promote tissue regeneration.

When a person develops ARDS, their lungs develop severe inflammation and buildup fluid in their lungs.

Ricordi said ARDS patients usually undergo invasive procedures, but thats not the case with these stem cells.

These cells injected in the IV naturally go with a very simple procedure that does not require any invasive procedure. You can just direct the transfusion to the lung, he explained. The cells go to the lungs and it has just been an amazing kind of result and we are very excited to move to the next step.

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Doctors Make Medical Breakthrough In Treating Severe Cases Of COVID - CBS San Francisco

Mana joins the hectic fight against solid tumors with an ‘off-the-shelf’ candidate angling for an IND this year – Endpoints News

The hunt for effective therapies for solid tumors has heated up in early 2021 with a string of biotechs touting big investor checks and name-brand collaborations to chase those hard-to-treat lumps. Now, with one of its candidates already in the clinic for leukemia, Mana Therapeutics is taking a new round of funding to join the fray.

On Friday, Mana unveiled a $35 million Series A financing round that will help push the Boston-area biotechs lead candidate through a Phase I trial and could help the company secure an IND for an off-the-shelf allogeneic molecule targeting transplant-ineligible AML and solid tumors within the year.

The biotechs leading molecule, dubbed MANA-312, is already engaged in the Phase I study of patients with acute myeloid leukemia, myelodysplastic syndrome after undergoing an allogenic hematopoietic stem cell transplantation. Manas goal is to use its technology to create an inventory of off-the-shelf allogeneic products that can treat the majority of patients with certain targeted cancer indications using whats called a human leukocyte antigen matching system.

Its a different take on a similar line of attack for solid tumors: using the bodys natural immune system to educate healthy cells already in the body to target antigens on the surface of the tumors cancer cells without damaging the otherwise healthy cells. To do this, Mana uses an in-house platform called EDIFY, which it says leverages natural immune system pathways to educate T cells to target multiple cell surfaces and intracellular tumor-associated antigens.

Through multiple antigen targeting processes, the companys technology is designed to prevent the tumors immune escape, and it says the allogeneic method which uses healthy donor cells to create a master cell bank and is then used for specific therapies of attacking the solid cancer tumors could provide superior efficacy to single antigen and other cell therapy approaches.

MANA-312 also isnt the biotechs only candidate in the works. MANA-412 is a preclinical off-the-shelf allogeneic cell therapy for treating transplant-ineligible acute myeloid leukemia and solid tumors and could be ready for an IND filing by the end of the year, Mana said. The Series A round will help fund preclinical development for that candidate as well.

Mana was founded based on research and human proof-of-concept clinical trials conducted by Catherine Bollard of Childrens National Hospital and her colleagues at Johns Hopkins Medical Center. Those trials, in both solid and hematologic tumors, supported a strong safety profile, showed immunological anti-tumor activity and validated MANAs initial set of tumor antigens, the company said. Then Bollard co-founded the company with industry vet Marc Cohen. Ex-Gilead exec Martin Silverstein is the CEO.

The human proof-of-concept trials conducted by my team and colleagues showed potential for a nonengineered approach to educating T-cells to attack multiple tumor antigens, which MANA is expanding even further through refinement of the manufacturing process for an allogeneic product and application to a broader set of antigens in a variety of clinical indications and settings, Bollard said in a statement.

MANAs $35 million financing round was led by Cobro Ventures and Lightchain Capital and joined by LifeSci Venture Partners with other undisclosed investors.

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Mana joins the hectic fight against solid tumors with an 'off-the-shelf' candidate angling for an IND this year - Endpoints News

Global CAR-T Pipeline Insight Report 2020: Overview, Landscape, Therapeutic Assessment, Current Treatment Scenario and Emerging Therapies -…

December 30, 2020 04:38 ET | Source: Research and Markets

Dublin, Dec. 30, 2020 (GLOBE NEWSWIRE) -- The "CAR-T - Pipeline Insight, 2020" drug pipelines has been added to ResearchAndMarkets.com's offering.

The "CAR-T - Pipeline Insight, 2020," report provides comprehensive insights about 250+ companies and 250+ pipeline drugs in CAR-T pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.

CAR-T: Overview

CAR-T is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. CAR T-cell therapy is used to treat certain blood cancers, and it is being studied in the treatment of other types of cancer. Also called chimeric antigen receptor T-cell therapy.

Potential Mechanisms of CAR-T Cell-Mediated Toxicity

Significant progress has been made in the field of cancer immunotherapy, and CAR-T cells have shown outstanding efficacy in clinical trials. As with all technologies, CAR-T technologies also need to go through a long process of development, and CAR-T cell therapy has related acute and chronic toxicities that have become a roadblock on the developmental path. If these setbacks are not overcome, it will be difficult to make a more significant breakthrough.

Cytokine Release Syndrome

Cytokine release syndrome (CRS) is the most common toxic side effect in CAR-T cell therapy. CRS is a systemic inflammatory response caused by the significant increase in cytokines accompanied by the rapid in vivo activation and proliferation of CAR-T cells, usually occurring within a few days after the first infusion. CRS is a clinical condition with mild symptoms of fever, fatigue, headache, rash, joint pain, and myalgia. Severe CRS cases are characterized by tachycardia, hypotension, and high fever. Mild to moderate CRS is usually self-limiting and can be managed through close observation and supportive care. Severe CRS must be treated with tocilizumab or steroids alone for intensive treatment.

Advances in Research of CAR-T Cell Therapy for Solid Tumors

Although early CAR-T cell trials of solid tumors did not show the same success as observed in leukemia trials, a better understanding of the multiple barriers seen in solid tumors could promote the design of clinical trials for CAR-T cells. In this early stage of clinical development, CAR-T cells offer much hope. The ability of genetic manipulation techniques to modify CAR-T cells provides almost unlimited opportunities for other changes and improvements, thus providing a strong desire for future success.

Global Landscape of CAR-T Cell Therapy

At present, CAR-T cells are widely used in cellular immunotherapy for various tumors. According to statistics, more than 300 clinical trials of CAR-T cell therapies have been approved by many national drug regulatory agencies, including the FDA of the United States. Statistical data from these clinical trials show that although the effects of various clinical trials vary due to the use of different sources and the preparation techniques of CARs and T cells, as well as differences in pretreatment and combinations of drugs, overall, CAR-T cells are effective in treating tumors with an effective rate of 30% to 70% or even more than 90%. For example, the complete remission rate for r/r ALL treated with the Novartis drug CTL0l9, which the FDA has approved, is 93%. Perhaps CAR-T cell therapy will ultimately remedy the fate of human cancer.

CAR-T Emerging Drugs Chapters

This segment of the CAR-T report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases.

CAR-T: Therapeutic Assessment

This segment of the report provides insights about the different CAR-T drugs segregated based on following parameters that define the scope of the report, such as:

Major Players in CAR-T

There are approx. 250+ key companies which are developing the therapies for CAR-T. The companies which have their CAR-T drug candidates in the most advanced stage, i.e. phase III include, Janssen Research & Development, ViiV Healthcare, Sorrento Therapeutics, Celgene, Novartis, Abbott etc.

Report Highlights

Current Treatment Scenario and Emerging Therapies:

Key Players

Key Products

For more information about this drug pipelines report visit https://www.researchandmarkets.com/r/c6ze76

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

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Global CAR-T Pipeline Insight Report 2020: Overview, Landscape, Therapeutic Assessment, Current Treatment Scenario and Emerging Therapies -...

Versiti Blood Centers and Noodles & Company Serve Up Thanks to Blood Donors – PRNewswire

MILWAUKEE, Dec. 30, 2020 /PRNewswire/ -- Versiti Blood Centers and premier partner Noodles & Company are dishing out discounts for life-saving donations during National Blood Donor Month this January.

Since 2016, Noodles & Company has supported Versiti's mission by aligning as a community partner and donating over $1.3 million in discounts and coupons to blood donors. Throughout January 2020, all attempting blood donors will receive a coupon redeemable for $4 off their order when they donate at a Versiti donor center or select community blood drive.

January is National Blood Donor Month, which highlights the critical need for blood during winter when donations often decline. Donors of all blood types are needed, but especially O negative blood donors who carry the universal blood type given to people in emergency situations.

To schedule an appointment, visit versiti.org.

About Versiti Blood Centers Versiti is a not-for-profit organization headquartered in Milwaukee that specializes in blood services, esoteric diagnostic testing, organ, tissue and stem cell donation, medical services and leading-edge research. Founded in 1947, Versiti is the primary provider of blood products and services for more than 250 hospitals in five midwestern states: Illinois, Indiana, Michigan, Ohio and Wisconsin. Versiti collects more than 602,000 units of blood each year at 35 permanent donation sites and more than 12,000 community blood drives. For more, visit versiti.org.

SOURCE Versiti, Inc.

https://www.versiti.org

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Versiti Blood Centers and Noodles & Company Serve Up Thanks to Blood Donors - PRNewswire

2020 health care year in review – Crain’s Cleveland Business

While COVID-19 was no doubt the story of the year, Northeast Ohio's health care scene grabbed headlines for several other reasons.

Cleveland Clinic and Aetna, a CVS Health Company (NYSE: CVS), announced they would launch a co-branded insurance plan. And Massachusetts-based Devoted Health launched in Ohio, offering Medicare Advantage plans across Cleveland, Akron, Canton and North-Central Ohio.

Also this year, Bravo Wellness became a wholly owned subsidiary of Medical Mutual at the start of January. Bravo, a Cleveland-based provider of employee wellness programs, this summer acquired Chicago-based PUSH Wellness.

The region's health systems continued their growth and consolidation trends of past decades.

Lake Health, which in early 2020 announced its search for a strategic partnership, reached an agreement to join University Hospitals, pending regulatory approval, the two announced in December.

The news came a month after UH announced it would gain a minority interest in Western Reserve Hospital, an independent, physician-owned hospital in Cuyahoga Falls. It will be UH's first inpatient presence in Summit County where hospital ownership has shifted dramatically in the past few years, including in 2015 when Cleveland Clinic acquired Akron General Health System.

At the start of 2020, Summa Health was taking steps toward becoming a subsidiary of Southfield, Mich.-based Beaumont Health, but the deal fell apart. After pausing the process to focus on COVID-19, Beaumont ultimately walked away from partnership plans in May.

Though the pandemic initially slowed down the due diligence process, Cleveland Clinic ultimately reached an agreement with Sisters of Charity for Mercy Medical Center in Canton to become a full member of Cleveland Clinic. The deal is expected to be finalized Feb. 1, pending regulatory approval.

The Clinic also worked to grow its research capacity, establishing two new research centers in April following more than a year of planning: The Center for Immunotherapy and Precision Immuno-Oncology and the Center for Global and Emerging Pathogens Research. This summer, the system also opened its 107,000-square-foot Florida Research and Innovation Center in Port St. Lucie, Fla., which will collaborate with researchers in Cleveland.

Meanwhile, MetroHealth continued its own expansions this year. Alongside the ongoing construction for its nearly $1 billion campus transformation, the system this year announced a $42 million project to expand the number of behavioral health beds in Cleveland Heights and a $9 million investment into its Old Brooklyn campus.

MetroHealth also received a $42 million gift the largest in its history from JoAnn and Bob Glick to support programs that aim to reverse health inequities and improve community health in Greater Cleveland.

In addition to the growth of its health systems, Northeast Ohio's health care options expanded with several newcomers to the region as the market and demand for outpatient health care continues to grow.

NewVista Healthcare, based in Blue Ash (outside Cincinnati), announced plans to open two new substance use disorder (SUD) treatment centers in the Cleveland area. Cincinnati-based Queen City Hospice announced plans to enter the Cleveland market with the launch of Miracle City Hospice. Nashville-based Spero Health opened three Northeast Ohio locations to offer addiction treatment services. This summer, Miami-based ChenMed began opening three planned facilities in the Cleveland area. And Chicago-based Oak Street Health, which began opening primary care centers in Northeast Ohio a couple of years ago, has continued its growth in the region in 2020.

This year has presented what we all hope will be once-in-a-lifetime challenges. It has also sparked collaborations and innovation across the health care industry and beyond. With a vaccine offering a light at the end of the tunnel, health care leaders are beginning to think about how to draw on deepened relationships in the next normal. In the meantime, they continue to ask everyone to wear their masks, practice social distancing. wash their hands and stay safe, especially this holiday season.

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2020 health care year in review - Crain's Cleveland Business

The Top 10 FDA Oncology Drug Approvals of 2020 – Curetoday.com

While 2020 had its share of negative healthcare headlines, the Food and Drug Administration (FDA) continued to push through approvals on a large number of oncology therapies throughout the year, from acute myeloid leukemia (AML) to breast cancer and beyond.

Heres a look back at 2020s top 10 most popular FDA drug approvals in the oncology space, as determined by CURE readers.

In August, the FDA approved the expansion of Kyprolis (carfilzomib) in combination to with Darzalex (daratumumab) plus dexamethasone in once- and twice-weekly dosing regimens for the treatment of patients with relapsed or refractory multiple myeloma who have received a maximum of three prior lines of therapy.

After granting it an accelerated approval in 2018, the Food and Drug Administration fully approved Venclexta (venetoclax) in combination with Vidaza (azacytidine), Dacogen (decitabine) or low dose cytarabine (LDAC) in newly diagnosed patients with AML aged 75 years or older in October.

The combination of Monjuvi (tafasitamab-cxix) and Revlimid (lenalidomide), approved in August, fills an unmet need for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are also unable to undergo autologous stem cell transplant, said Dr. Gilles Salles.

The targeted drug Qinlock (ripretinib), which interferes with the activity of proteins that drive gastrointestinal stromal tumor (GIST), was approved by the FDA in May for patients with advanced disease that has progressed despite treatment with other kinase inhibitors.

The FDAs approval of Braftovi (encorafenib) and Erbitux (cetuximab) with or without Mektovi (binimetinib) for adults with metastatic colorectal cancer (CRC) with a BRAF V600E mutation is a welcomed approval, according to Dr. Richard Goldberg, because patients with this mutation have a poorer than average prognosis and more limited treatment options than other colorectal cancer patients. Having an effective, rationally designed regimen for them that attacks multiple points in the pathway that drives their tumor was sorely needed, said Goldberg.

In May, the FDA approved Retevmo (selpercatinib), the first of its kind, to treat non-small cell lung cancer (NSCLC), medullary thyroid cancer and other types of thyroid cancers with rearranged during transfection, or RET, alterations. The kinase inhibitor blocks a type of enzyme and helps prevent cancer cells from growing.

The FDA approved and granted priority review in September to Gavreto (pralsetinib) for the treatment of patients with metastatic, RET fusion-positive NSCLC. The FDA approval of Gavreto for RET fusion-positive non-small cell lung cancer is an important step towards our goal of providing an effective treatment option for every person diagnosed with lung cancer, no matter how rare or hard-to-treat their type of disease, said Dr. Levi Garraway, Genentechs chief medical officer and head of Global Product Development, in a statement.

The Food and Drug Administrations May approval of the first antibody-drug conjugate to treat patients with pretreated metastatic triple-negative breast cancer was a major milestone, according to Dr. Aditya Bardia, a breast medical oncologist at Massachusetts General Hospital Cancer Center.

This approval in April was big news for patients with a variety of adult cancers. The important social distancing measures for COVID-19 have created a number of challenges for people with cancer, including keeping to planned treatment schedules, Dr. Roy Baynes, senior vice president, head of global clinical development and chief medical officer at Merck Research Laboratories, said in a press release. Todays approval of an every-six-weeks dosing schedule for Keytruda gives doctors an option to reduce how often patients are at the clinic for their treatment.

Our most popular approval coverage for the combination of Nerlynx and Xeloda in February comes off the heels of the phase 3 NALA trial that looked at the efficacy of Nerlynx in combination with Xeloda, which found a significant improvement in patients progression free survival (the time from treatment to disease progression or worsening) compared to Tykerb (lapatinib) in combination with Xeloda.

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The Top 10 FDA Oncology Drug Approvals of 2020 - Curetoday.com

Gut microbiota: How does it interact with the brain? – Medical News Today

Through studies in mice, researchers find evidence that having a healthful balance of gut microorganisms is important for good health.

Researchers from the Institut Pasteur, French National Center for Scientific Research (CNRS), and Inserm have found evidence that gut microbiota also plays a role in mood regulation and brain function.

Gut microbiota is the community of bacteria, fungi, and viruses that live in the digestive tract.

These findings in mice suggest that changes to gut bacterial communities may lead or contribute to depression. If humans have a similar mechanism, doctors might be able to use bacteria strains to treat mood disorders, such as depression.

A group of 16 researchers from several prominent French research institutions conducted the study, which appears in Nature Communications.

Studies have found that some people with depression experience dysbiosis, which is an imbalance or change in their intestinal microbiota.

Research conducted on rodents also shows that gut dysbiosis has associations with neurological changes linked with depression, such as:

Animal studies also show that gut microbiota helps regulate anxiety. It may also influence the development of neurological conditions caused by circuit dysfunctions, such as Parkinsons disease, Alzheimers disease, depression, and obsessive-compulsive disorder.

Researchers think this is because gut bacteria release metabolites, tiny bits of food broken down by digestion that influence brain function. Metabolites may impact mood regulation by acting on the endocannabinoid system.

The endocannabinoid system is a complex cell-signaling system consisting of lipid (fat)-based neurotransmitters and their receptors.

It is found throughout the body and plays a role in important aspects of health, such as immune and nervous system function and cellular communication in the nervous system. It also regulates emotions, moods, and stress responses by activation of the systems main receptor, CB1.

Previous research supports the idea that restoring gut microbial health may help treat depression. In animal studies, prebiotic treatment influenced emotional behavior. In human studies, prebiotic supplementation also improved mood in people with depression.

But despite educated theories, researchers still do not know precisely how gut bacteria impact brain function.

Researchers in the recent study set out to find the mechanisms linking gut microbiota and mood disorders. A team of researchers from some of these same French institutions published a report earlier this year, which found that stress-induced changes in gut microbiota reduced the efficacy of the antidepressant fluoxetine in mice.

In the study, researchers submitted genetically identical mice to unpredictable chronic mild stress (UCMS), a mouse model of stress-induced depression, for 8 weeks.

This treatment caused the mice to develop depressive-like behaviors, such as reduced eating, grooming, weight loss, and hippocampal neurogenesis. The hippocampus is responsible for learning and memory and is heavily affected by several psychiatric and neurological conditions.

Researchers then transplanted fecal samples containing gut microbiota from control and UCMS-exposed mice into healthy mice. To serve as a control, mice that received fecal transplants were germ-free mice or received treatment with antibiotics for 6 days.

After 8 weeks, mice that received transplants from UCMS mice developed depression-like symptoms. The mice also experienced a reduction in the number of new brain stem cells and neurons in their hippocampus.

These findings show that transferring gut microbiota from stress-induced depressive mice to healthy mice induced depression-like behaviors.

Surprisingly, simply transferring the microbiota from an animal with mood disorders to an animal in good health was enough to bring about biochemical changes and confer depressive-like behaviors in the latter.

Pierre-Marie Lledo, head of the Perception and Memory Unit at the Institut Pasteur (CNRS/Institut Pasteur), joint last author of the study

To figure out how this occurred, researchers explored the possibility that UCMS-exposed microbiota may trigger depression by altering metabolism. They found that mice with UCMS microbiota had significantly reduced levels of certain fatty acids in their blood and brain.

The reduced fatty acids included monoacylglycerols (MAG), diacylglycerols (DAG), polyunsaturated fatty acid (PUFA), and linoleic acid. monoacylglycerols (MAG), diacylglycerols (DAG), polyunsaturated fatty acid (PUFA), and linoleic acid. Variations of two of these fatty acids, DAD and PUFA, are converted into endocannabinoids (eCB).

The researchers speculate that gut dysbiosis may cause these changes in fatty acid levels. Studies link the dysregulation of the endocannabinoid system and its central receptor, CB1, with depression in both UCMS-model mice and humans.

In the study, the researchers found that mice with UCMS microbiota had greatly reduced levels of eCBs in their hippocampus and blood. They also found that mice with UCMS microbiota had reduced levels of Lactobacillus bacteria.

The researchers were able to reduce the depressive impact of the UCMS microbiota by enhancing CB1 levels and giving the mice a strain of Lactobacillus bacteria orally.

These findings suggest that chronic stress, diet, and the gut microbiota contribute to the development of depression-like behaviors via the endocannabinoid system.

This discovery shows the role played by the gut microbiota in normal brain function, says Grard Eberl, Head of the Microenvironment and Immunity Unit (Institut Pasteur/Inserm) and joint last author of the study.

More specifically, imbalances in the gut bacterial community that reduce fatty acid levels vital to the endocannabinoid system and brain function seem to encourage the development of depression-like behaviors.

These findings mean certain bacteria could act as a natural antidepressant, treating mood disorders by restoring gut microbial health. And this is promising news, considering the slew of potential adverse side effects and relatively low efficacy rate of most current antidepressants.

To confirm their results, the researchers will need to test their findings in humans. The researchers say that new research will also need to explore whether changes to the gut microbiota impact other brain targets of the endocannabinoid system in the same way.

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Gut microbiota: How does it interact with the brain? - Medical News Today