Category Archives: Cell Therapy

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Atara Biotherapeutics Announces Preliminary Results for ATA2271, a Next-Generation Autologous Mesothelin-targeted CAR T-cell Therapy for Solid Tumors,...

Data on small, hypo-immune CRISPR systems show efficient edits in vivo in pre-clinical study

Novel gene editing systems are shown to enable efficient and specific edits in T cells, NK cells, and B cells

EMERYVILLE, Calif., December 08, 2021--(BUSINESS WIRE)--Metagenomi, a genetic medicines company with a versatile portfolio of next-generation gene editing tools, today announced that the company will share data related to their novel, compact, and hypo-immune gene editing systems at the 63rd Annual Meeting and Exposition of the American Society of Hematology (ASH), which is taking place in Atlanta, GA and virtually, December 1114.

"The development of CAR T therapies and other genetically engineered cell therapies in recent years has resulted in significant benefits for patients, yet there remains a large unmet need for gene editing systems that can be used to develop novel immunotherapy approaches to treat blood cancers," said Brian C. Thomas, PhD, CEO and Co-Founder of Metagenomi. "At ASH, we are presenting data on our novel nucleases that display highly efficient and specific gene editing both in vivo and ex vivo and hold significant potential to drive the development of new and efficacious therapies for patients."

In a poster titled "A Novel Type V CRISPR System with Potential for Genome Editing in the Liver," it is shown that Metagenomis novel Type V CRISPR-associated nuclease was highly active in the liver of mice when systemically administered via lipid nanoparticles (LNP). The nuclease was derived from a unique natural environment and is phylogenetically distinct from previously identified Type V systems. Moreover, no antibodies to the nuclease were detected in serum from 50 healthy human donors, while between one third and half of the same serum samples contained antibodies that bind to spCas9, which is derived from a Streptococcus bacteria that commonly infects humans. In summary, this novel Type V CRISPR-associated nuclease is a promising new gene editing system for in vivo editing of the liver.

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In a separate poster titled "Novel CRISPR-Associated Gene Editing Systems Discovered in Metagenomic Samples Enable Efficient and Specific Genomic Engineering for Cell Therapy Development," three novel gene editing systems were used to make reproducible and efficient edits to human immune cells, demonstrating utility for the next generation of cell therapy development for blood cancers. Metagenomis novel gene editing systems were used to disrupt the T cell receptor alpha-chain constant region and the T cell receptor beta-chain constant region in approximately 90 percent of cells. Beta-2 microglobulin was edited in 95 percent of T cells. A chimeric antigen receptor (CAR) construct was also shown to be integrated in up to 60 percent of T cells. Novel gene editing systems were deployed in NK cells to disrupt CD38 a cell surface immune modulator that can be targeted in the development of cancer immunotherapy and to integrate a CAR construct that led to robust CAR-directed cellular cytotoxicity. B cell editing occurred in approximately 80% of target cells with successful transgene integration. Whats more, as these gene editing systems are taken from environmental samples as opposed to human pathogens, pre-existing immunity is expected to be rare. In summary, these novel systems were shown to result in highly efficient and specific gene edits in human immune cells and display the potential for use in cell therapy development.

Details of the presentations are below:

Presentation Title: A Novel Type V CRISPR System with Potential for Genome Editing in the LiverSession Title: 801. Gene Therapies: Poster IPresenting Author: Morayma Temoche-Diaz, PhDPublication Number: 1862 Session Time: Saturday, December 11, 5:30 p.m. ET

Presentation Title: Novel CRISPR-Associated Gene-Editing Systems Discovered in Metagenomic Samples Enable Efficient and Specific Genome Engineering for Cell Therapy DevelopmentSession Title: 801. Gene Therapies: Poster IIIPresenting Author: Gregory Cost, PhD, Vice President of Biology, MetagenomiPublication Number: 3984 Session Time: Monday, December 13, 6:00 8:00 p.m. ET

About Metagenomi

Metagenomi is a gene editing company committed to developing potentially curative therapeutics by leveraging a proprietary toolbox of next-generation gene editing systems to accurately edit DNA where current technologies cannot. Our metagenomics-powered discovery platform and analytical expertise reveal novel cellular machinery sourced from otherwise unknown organisms. We adapt and forge these naturally evolved systems into powerful gene editing systems that are ultra-small, extremely efficient, highly specific and have a decreased risk of immune response. These systems fuel our pipeline of novel medicines and can be leveraged by partners. Our goal is to revolutionize gene editing for the benefit of patients around the world. For more information, please visit https://metagenomi.co/.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211208005131/en/

Contacts

Metagenomi

Investor:Simon HarnestCIO, SVP Strategysimon@metagenomi.co (917) 403-1051

Media:Ashlye HodgeSr. Marketing and Communications Specialistashlye@metagenomi.co (510) 734-4409

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Metagenomi to Present Preclinical In Vivo and Ex Vivo Gene-Editing Data at the 63rd American Society of Hematology (ASH) Annual Meeting - Yahoo...

Submission based on data from pivotal CARTITUDE-1 trial

SOMERSET, N.J., December 07, 2021--(BUSINESS WIRE)--Legend Biotech Corporation (NASDAQ: LEGN), a global, clinical-stage biotechnology company developing and manufacturing novel therapies, announced today the submission of a New Drug Application (NDA) to the Japanese Ministry of Health, Labour and Welfare (MHLW) for ciltacabtagene autoleucel (cilta-cel) by its collaboration partner, Janssen Pharmaceutical K.K. (Janssen). Cilta-cel is an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR)-T cell therapy for the treatment of adults with relapsed or refractory multiple myeloma who have received at least three prior therapies, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 antibody.

The submission is based on results from the Phase 1b/2 CARTITUDE-1 study conducted in the US and Japan, which evaluated the efficacy and safety of cilta-cel for patients with relapsed or refractory multiple myeloma.1 Cilta-cel is currently under regulatory review by several health authorities around the world, including the United States and Europe.

"Todays submission is an encouraging step in our mission to provide a potentially transformative cell therapy option to patients with multiple myeloma," said Ying Huang, PhD, CEO and CFO of Legend Biotech. "We look forward to closely collaborating with our partner Janssen and the MHLW in order to make cilta-cel available to patients living with relapsed or refractory multiple myeloma, who have exhausted several standard-of-care treatments and are facing poor prognoses."

About Ciltacabtagene Autoleucel

Cilta-cel is an investigational chimeric antigen receptor T cell (CAR-T) therapy, formerly identified as JNJ-4528 in the U.S. and Europe and LCAR-B38M CAR-T cells in China, that is being studied in a comprehensive clinical development program for the treatment of patients with relapsed or refractory multiple myeloma and in earlier lines of treatment. The design consists of a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies. In December 2017, Legend Biotech, Inc. entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel. In addition to a Breakthrough Therapy Designation (BTD) granted in the U.S. in December 2019, cilta-cel received a Priority Medicines (PRiME) designation from the European Commission in April 2019, and a BTD in China in August 2020. In addition, Orphan Drug Designation was granted for cilta-cel by the U.S. FDA in February 2019, and by the European Commission in February 2020. A Biologics License Application seeking approval of cilta-cel was submitted to the U.S. FDA and a Marketing Authorization Application was submitted to the European Medicines Agency.

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About the CARTITUDE-1 Study

CARTITUDE-1 (NCT03548207) is a Phase 1b/2, open-label, multicenter study evaluating the safety and efficacy of cilta-cel in adults with relapsed or refractory with multiple myeloma who have received at least 3 prior lines of therapy or are double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), received a PI, an IMiD, and anti-CD38 antibody and documented disease progression within 12 months of starting the most recent therapy.1

About Multiple Myeloma

Multiple myeloma, an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.2 In Japan, there were more than 7,000 new cases of multiple myeloma and nearly 5,000 deaths.3 Although treatment may result in remission, most patients experience relapse.4 Relapsed myeloma is when the disease has returned after a period of initial, partial or complete remission and does not meet the definition of being refractory.5 Refractory multiple myeloma is when a patients disease is non-responsive or progresses within 60 days of their last therapy.6,7 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed by symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.8 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and few treatment options available.9

About Legend Biotech

Legend Biotech is a global, clinical-stage cell therapy company dedicated to treating, and one day curing, life-threatening diseases. Headquartered in Somerset, New Jersey, we are developing a diverse array of technology platforms, including autologous and allogenic chimeric antigen receptor T-cell, T-cell receptor (TCR-T), and natural killer (NK) cell-based immunotherapy. From our three R&D sites around the world, we apply these innovative technologies to pursue the discovery of safe, efficacious and cutting-edge options for patients worldwide. We are currently engaged in a strategic collaboration to develop and commercialize our lead product candidate, ciltacabtagene autoleucel, an investigational BCMA-targeted CAR-T cell therapy for patients living with multiple myeloma. This candidate is being studied in registrational clinical trials and has received priority review from the U.S. Food and Drug Administration for the first indication.

Learn more at http://www.legendbiotech.com and follow us on Twitter and LinkedIn.

Cautionary Note Regarding Forward-Looking Statements

Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, constitute "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to Legend Biotechs strategies and objectives, the anticipated timing of, and ability to progress, clinical trials, the clinical data relating to the CARTITUDE Development Program and the potential benefits of our product candidates. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors. Legend Biotechs expectations could be affected by, among other things, uncertainties involved in the development of new pharmaceutical products; unexpected clinical trial or preclinical study results, including as a result of additional analysis of existing data or unexpected new data; unexpected regulatory actions or delays, including requests for additional safety and/or efficacy data or analysis of data, or government regulation generally; unexpected delays as a result of actions undertaken, or failures to act, by our third party partners; uncertainties arising from challenges to Legend Biotechs patent or other proprietary intellectual property protection, including the uncertainties involved in the US litigation process; competition in general; government, industry, and general public pricing and other political pressures; the duration and severity of the COVID-19 pandemic and governmental and regulatory measures implemented in response to the evolving situation; as well as the other factors discussed in the "Risk Factors" section of Legend Biotechs Annual Report on Form 20-F filed with the Securities and Exchange Commission on April 2, 2021. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described in this press release as anticipated, believed, estimated or expected. Legend Biotech specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

Source: Legend Biotech

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1 A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1). Available at: https://clinicaltrials.gov/ct2/show/NCT03548207. Accessed December 2021.

2 American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction. Accessed December 2021.

3 World Health Organization International Agency for Research on Cancer (IARC). GLOBOCAN 2020: Japan Fact Sheet. https://gco.iarc.fr/today/data/factsheets/populations/392-japan-fact-sheets.pdf. Accessed December 2021.

4 Abdi J, Chen G, Chang H, et al. Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms. Oncotarget. 2013;4:21862207.

5 National Cancer Institute. NCI dictionary of cancer terms: relapsed. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=45866. Accessed December 2021.

6 National Cancer Institute. NCI dictionary of cancer terms: refractory. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=350245. Accessed November 2020.

7 Richardson P, Mitsiades C, Schlossman R, et al. The treatment of relapsed and refractory multiple myeloma. Hematology Am Soc Hematol Educ Program. 2007:317-23.

8 American Cancer Society. Multiple myeloma: early detection, diagnosis and staging. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8740.00.pdf. Accessed November 2020.

9 Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012;26:149-57.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211207005756/en/

Contacts

Investor Contacts: Joanne Choi, Senior Manager of Investor Relations and Corporate Communications, Legend Biotechjoanne.choi@legendbiotech.com or investor@legendbiotech.com

Crystal Chen, Manager of Investor Relations and Corporate Communications, Legend Biotechcrystal.chen@legendbiotech.com

Press Contact: Tina Carter, Corporate Communications Lead, Legend Biotechtina.carter@legendbiotech.com (908) 331-5025

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Legend Biotech Announces Submission of New Drug Application to Japanese Regulatory Authority for BCMA CAR-T Therapy Cilta-cel for the Treatment of...

J Cardiovasc Nurs. Author manuscript; available in PMC 2014 Jul 21.

Published in final edited form as:

PMCID: PMC4104807

NIHMSID: NIHMS100185

1Department of Bioengineering, University of Illinois at Chicago

2Department of Physiology and Biophysics and Department of Bioengineering, University of Illinois at Chicago

1Department of Bioengineering, University of Illinois at Chicago

2Department of Physiology and Biophysics and Department of Bioengineering, University of Illinois at Chicago

Stem cells have the ability to differentiate into specific cell types. The two defining characteristics of a stem cell are perpetual self-renewal and the ability to differentiate into a specialized adult cell type. There are two major classes of stem cells: pluripotent that can become any cell in the adult body, and multipotent that are restricted to becoming a more limited population of cells. Cell sources, characteristics, differentiation and therapeutic applications are discussed. Stem cells have great potential in tissue regeneration and repair but much still needs to be learned about their biology, manipulation and safety before their full therapeutic potential can be achieved.

Stem cells have the ability to build every tissue in the human body, hence have great potential for future therapeutic uses in tissue regeneration and repair. In order for cells to fall under the definition of stem cells, they must display two essential characteristics. First, stem cells must have the ability of unlimited self-renewal to produce progeny exactly the same as the originating cell. This trait is also true of cancer cells that divide in an uncontrolled manner whereas stem cell division is highly regulated. Therefore, it is important to note the additional requirement for stem cells; they must be able to give rise to a specialized cell type that becomes part of the healthy animal.1

The general designation, stem cell encompasses many distinct cell types. Commonly, the modifiers, embryonic, and adult are used to distinguish stem cells by the developmental stage of the animal from which they come, but these terms are becoming insufficient as new research has discovered how to turn fully differentiated adult cells back into embryonic stem cells and, conversely, adult stem cells, more correctly termed somatic stem cells meaning from the body, are found in the fetus, placenta, umbilical cord blood and infants.2 Therefore, this review will sort stem cells into two categories based on their biologic properties - pluripotent stem cells and multipotent stem cells. Their sources, characteristics, differentiation and therapeutic applications are discussed.

Pluripotent stem cells are so named because they have the ability to differentiate into all cell types in the body. In natural development, pluripotent stem cells are only present for a very short period of time in the embryo before differentiating into the more specialized multipotent stem cells that eventually give rise to the specialized tissues of the body (). These more limited multipotent stem cells come in several subtypes: some can become only cells of a particular germ line (endoderm, mesoderm, ectoderm) and others, only cells of a particular tissue. In other words, pluripotent cells can eventually become any cell of the body by differentiating into multipotent stem cells that themselves go through a series of divisions into even more restricted specialized cells.

During natural embryo development, cells undergo proliferation and specialization from the fertilized egg, to the blastocyst, to the gastrula during natural embryo development (left side of panel). Pluripotent, embryonic stem cells are derived from the inner cell mass of the blastoctyst (lightly shaded). Multipotent stem cells (diamond pattern, diagonal lines, and darker shade) are found in the developing gastrula or derived from pluripotent stem cells and are restricted to give rise to only cells of their respective germ layer.

Based on the two defining characteristics of stem cells (unlimited self-renewal and ability to differentiate), they can be described as having four outcomes or fates3 (). A common fate for multipotent stem cells is to remain quiescent without dividing or differentiating, thus maintaining its place in the stem cell pool. An example of this is stem cells in the bone marrow that await activating signals from the body. A second fate of stem cells is symmetric self-renewal in which two daughter stem cells, exactly like the parent cell, arise from cell division. This does not result in differentiated progeny but does increase the pool of stem cells from which specialized cells can develop in subsequent divisions. The third fate, asymmetric self-renewal, occurs when a stem cell divides into two daughter cells, one a copy of the parent, the other a more specialized cell, named a somatic or progenitor cell. Asymmetric self-renewal results in the generation of differentiated progeny needed for natural tissue development/regeneration while also maintaining the stem cell pool for the future. The fourth fate is that in which a stem cell divides to produce two daughters both different from the parent cell. This results in greater proliferation of differentiated progeny with a net loss in the stem cell pool.

Four potential outcomes of stem cells. A) Quiescence in which a stem cell does not divide but maintains the stem cell pool. B) Symmetric self-renewal where a stem cell divides into two daughter stem cells increasing the stem cell pool. C) Asymmetric self-renewal in which a stem cell divides into one differentiated daughter cell and one stem cell, maintaining the stem cell pool. D) Symmetric division without self-renewal where there is a loss in the stem cell pool but results in two differentiated daughter cells. (SC- Stem cell, DP-Differentiated progeny)

The factors that determine the fate of stem cells is the focus of intense research. Knowledge of the details could be clinically useful. For example, clinicians and scientists might direct a stem cell population to expand several fold through symmetrical self-renewal before differentiation into multipotent or more specialized progenitor cells. This would ensure a large, homogeneous population of cells at a useful differentiation stage that could be delivered to patients for successful tissue regeneration.

Pluripotent stem cells being used in research today mainly come from embryos, hence the name, embryonic stem cells. Pre-implantation embryos a few days old contain only 10-15% pluripotent cells in the inner cell mass (). Those pluripotent cells can be isolated, then cultured on a layer of feeder cells which provide unknown cues for many rounds of proliferation while sustaining their pluripotency.

Recently, two different groups of scientists induced adult cells back into the pluripotent state by molecular manipulation to yield induced pluripotent stem cells (iPS) that share some of the same characteristics as embryonic stem cells such as proliferation, morphology and gene expression (in the form of distinct surface markers and proteins being expressed).4-8 Both groups used retroviruses to carry genes for transcription factors into the adult cells. These genes are transcribed and translated into proteins that regulate the expression of other genes designed to reprogram the adult nucleus back into its embryonic state. Both introduced the embryonic transcription factors known as Sox2 and Oct4. One group also added Klf4 and c-Myc4, and the other group added Lin28 and Nanog.6 Other combinations of factors would probably also work, but, unfortunately, neither the retroviral carrier method nor the use of the oncogenic transcription factor c-Myc are likely to be approved for human therapy. Consequently, a purely chemical approach to deliver genes into the cells, and safer transcription factors are being tried. Results of these experiments look promising.9

Multipotent stem cells may be a viable option for clinical use. These cells have the plasticity to become all the progenitor cells for a particular germ layer or can be restricted to become only one or two specialized cell types of a particular tissue. The multipotent stem cells with the highest differentiating potential are found in the developing embryo during gastrulation (day 14-15 in humans, day 6.5-7 in mice). These cells give rise to all cells of their particular germ layer, thus, they still have flexibility in their differentiation capacity. They are not pluripotent stem cells because they have lost the ability to become cells of all three germ layers (). On the low end of the plasticity spectrum are the unipotent cells that can become only one specialized cell type such as skin stem cells or muscle stem cells. These stem cells are typically found within their organ and although their differentiation capacity is restricted, these limited progenitor cells play a vital role in maintaining tissue integrity by replenishing aging or injured cells. There are many other sub-types of multipotent stem cells occupying a range of differentiation capacities. For example, multipotent cells derived from the mesoderm of the gastrula undergo a differentiation step limiting them to muscle and connective tissue; however, further differentiation results in increased specialization towards only connective tissue and so on until the cells can give rise to only cartilage or only bone.

Multipotent stem cells found in bone marrow are best known, because these have been used therapeutically since the 1960s10 (their potential will be discussed in greater detail in a later section). Recent research has found new sources for multipotent stem cells of greater plasticity such as the placenta and umbilical cord blood.11 Further, the heart, until recently considered void of stem cells, is now known to contain stem cells with the potential to become cardiac myocytes.12 Similarly, neuro-progenitor cells have been found within the brain.13

The cardiac stem cells are present in such small numbers, that they are difficult to study and their function has not been fully determined. The second review in this series will discuss their potential in greater detail.

Since Federal funding for human embryonic stem cells is restricted in the United States, many scientists use the mouse model instead. Besides their ability to self-renew indefinitely and differentiate into cell types of all three germ layers, murine and human pluripotent stem cells have much in common. It should not be surprising that so many pluripotency traits are conserved between species given the shared genomic sequences and intra-cellular structure in mammals. Both mouse and human cells proliferate indefinitely in culture, have a high nucleus to cytoplasm ratio, need the support of growth factors derived from other live cells, and display similar surface antigens, transcription factors and enzymatic activity (i.e. high alkaline phosphatase activity).14 However, differences between mouse and human pluripotent cells, while subtle, are very important. Although the transcription factors mentioned above to induce pluripotency from adult cells (Oct3/4 and Sox2) are shared, the extracellular signals needed to regulate them differ. Mouse embryonic stem cells need the leukemia inhibitory factor and bone morphogenic proteins while human require the signaling proteins Noggin and Wnt for sustained pluripotency.15 Surface markers used to identify pluripotent cells also differ slightly between the two species as seen in the variants of the adhesion molecule SSEA (SSEA-1 in mouse, SSEA-3 & 4 in humans).16 Thus, while pluripotency research in mouse cells is valuable, a direct correlation to the human therapy is not likely.

Last, but certainly not least, a big difference between mouse and human stem cells are the moral and ethical dilemmas that accompany the research. Some people consider working with human embryonic stem cells to be ethically problematic while very few people have reservations on working with the mouse models. However, given the biological differences between human and mouse cells, most scientists believe that data relevant for human therapy will be missed by working only on rodents.

Cell surface markers are typically also used to identify multipotent stem cells. For example, mesenchymal stem cells can be purified from the whole bone marrow aspirate by eliminating cells that express markers of committed cell types, a step referred to as lineage negative enrichment, and then further separating the cells that express the sca-1 and c-Kit surface markers signifying mesenchymal stem cells. Both the lineage negative enrichment step and the sca-1/c-Kit isolation can be achieved by using flow cytometry and is discussed in further detail in the following review. The c-Kit surface marker also is used to distinguish the recently discovered cardiac stem cells from the rest of the myocardium. A great deal of recent work in cardiovascular research has centered on trying to find which markers indicate early multipotent cells that will give rise to pre-cardiac myocytes. Cells with the specific mesodermal marker, Kdr, give rise to the progenitor cells of the cardiovascular system including contracting cardiac myocytes, endothelial cells and vascular smooth muscle cells and are therefore considered to be the earliest cells with specification towards the cardiovascular lineage.17 Cells at this early stage still proliferate readily and yet are destined to become cells of the cardiovascular system and so may be of great value therapeutically.

Scientists are still struggling to reliably direct differentiation of stem cells into specific cell types. They have used a virtual alphabet soup of incubation factors toward that end (including trying a variety of growth factors, chemicals and complex substrates on which the cells are grown), with, so far, only moderate success. As an example of this complexity, one such approach to achieve differentiation towards cardiac myocytes is to use the chemical activin A and the growth factor BMP-4. When these two factors are administered to pluripotent stem cells in a strictly controlled manner, both in concentration and temporally, increased efficiency is seen in differentiation towards cardiac myocytes, but still, only 30% of cells can be expected to become cardiac.18

Multipotent cells have also been used as the starting point for cell therapy, again with cocktails of growth factors and/or chemicals to induce differentiation toward a specific, desired lineage. Some recipes are simple, such as the use of retinoic acid to induce mesenchymal stem cells into neuronal cells,19 or transforming growth factor- to make bone marrow-derived stem cells express cardiac myocyte markers.20 Others are complicated or ill-defined such as addition of the unknown factors secreted by cells in culture. Physical as well as chemical cues cause differentiation of stem cells. Simply altering the stiffness of the substrate on which cells are cultured can direct stem cells to neuronal, myogenic or osteogenic lineages.21 Cells evolve in physical and chemical environments so a combination of both will probably be necessary for optimal differentiation of stem cells. The importance of physical cues in the cells environment will be discussed in greater detail in the final review of this series. Ideally, for stem cells to be used therapeutically, efficient, uniform protocols must be established so that cells are a well-controlled and well-defined entity.

Pluripotent stem cells have not yet been used therapeutically in humans because many of the early animal studies resulted in the undesirable formation of unusual solid tumors, called teratomas. Teratomas are made of a mix of cell types from all the early germ layers. Later successful animal studies used pluripotent cells modified to a more mature phenotype which limits this proliferative capacity. Cells derived from pluripotent cells have been used to successfully treat animals. For example, animals with diabetes have been treated by the creation of insulin-producing cells responsive to glucose levels. Also, animals with acute spinal cord injury or visual impairment have been treated by creation of new myelinated neurons or retinal epithelial cells, respectively. Commercial companies are currently in negotiations with the FDA regarding the possibility of advancing to human trials. Other animal studies have been conducted to treat several maladies such as Parkinsons disease, muscular dystrophy and heart failure.18,22,23

Scientists hope that stem cell therapy can improve cardiac function by integration of newly formed beating cardiac myocytes into the myocardium to produce greater force. Patches of cardiac myocytes derived from human embryonic stem cells can form viable human myocardium after transplantation into animals,24 with some showing evidence of electrical integration.25,26 Damaged rodent hearts showed slightly improved cardiac function after injection of cardiac myocytes derived from human embryonic stem cells.21 The mechanisms for the gain in function are not fully understood but it may be only partially due to direct integration of new beating heart cells. It is more likely due to paracrine effects that benefit other existing heart cells (see next review).

Multipotent stem cells harvested from bone marrow have been used since the 1960s to treat leukemia, myeloma and lymphoma. Since cells there give rise to lymphocytes, megakaryocytes and erythrocytes, the value of these cells is easily understood in treating blood cancers. Recently, some progress has been reported in the use of cells derived from bone marrow to treat other diseases. For example, the ability to form whole joints in mouse models27 has been achieved starting with mesenchymal stem cells that give rise to bone and cartilage. In the near future multipotent stem cells are likely to benefit many other diseases and clinical conditions. Bone marrow-derived stem cells are in clinical trials to remedy heart ailments. This is discussed in detail in the next review of this series.

Pluripotent and multipotent stem cells have their respective advantages and disadvantages. The capacity of pluripotent cells to become any cell type is an obvious therapeutic advantage over their multipotent kin. Theoretically, they could be used to treat diseased or aging tissues in which multipotent stem cells are insufficient. Also, pluripotent stem cells proliferate more rapidly so can yield higher numbers of useful cells. However, use of donor pluripotent stem cells would require immune suppressive drugs for the duration of the graft28 while use of autologous multipotent stem cells (stem cells from ones self) would not. This ability to use ones own cells is a great advantage of multipotent stem cells. The immune system recognizes specific surface proteins on cells/objects that tell them whether the cell is from the host and is healthy. Autologous, multipotent stem cells have the patients specific surface proteins that allow it to be accepted by the hosts immune system and avoid an immunological reaction. Pluripotent stem cells, on the other hand, are not from the host and therefore, lack the proper signals required to stave off rejection from the immune system. Research is ongoing trying to limit the immune response caused by pluripotent cells and is one possible advantage that iPS cells may have.

The promises of cures for human ailments by stem cells have been much touted but many obstacles must still be overcome. First, more human pluripotent and multipotent cell research is needed since stem cell biology differs in mice and men. Second, the common feature of unlimited cell division shared by cancer cells and pluripotent stem cells must be better understood in order to avoid cancer formation. Third, the ability to acquire large numbers of the right cells at the right stage of differentiation must be mastered. Fourth, specific protocols must be developed to enhance production, survival and integration of transplanted cells. Finally, clinical trials must be completed to assure safety and efficacy of the stem cell therapy. When it comes to stem cells, knowing they exist is a long way from using them therapeutically.

Supported by NIH (HL 62426 and T32 HL 007692)

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Introduction to Stem Cell Therapy - PubMed Central (PMC)

HUMAN CELLS AND TISSUE PRODUCTS (HCT/P) REGULATIONS

According to FDA 21 CFR 1271, an HCT/P is regulated solely under section 361 of the PHS Act and the regulations in this part if it meets all of the following criteria:

(1) The HCT/P is minimally manipulated;

(2) The HCT/P is intended for homologous use only, as reflected by the labeling, advertising, or other indications of the manufacturer's objective intent;

(3) The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/P; and

(4) Either: (i) The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; or (ii) The HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and: (a) Is for autologous use; (b) Is for allogeneic use in a first-degree or second-degree blood relative; or (c) Is for reproductive use.

To learn more about FDA Regulations, please visit the following link: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=1271

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What is Stem Cell Therapy?

Mesenchymal Stem Cell Therapy

At Dream Body Clinic we offer Mesenchymal Stem Cell Therapy Treatments for Autoimmune disorders, Chronic Degenerative disorders, Articulations, Cosmetic Issues and more.

What kind of stem cells are these?

Our Mesenchymal Stem Cells are derived from Umbilical cord (Wharton Jelly) and Placenta. All donors are under 30 years old and put through a stringent screening process to ensure we only have gold quality stem cells. This tissue that we derive from is the youngest possible source for stem cells. This means that the stem cells we administer are as young and healthy as possible. There is no chance of rejection as mesenchymal stem cells lack human leukocyte antigen (HLA). HLA is what the immune system looks for to detect intruders. Our stem cells are sourced in the best way possible and then cultivated to provide the tens of millions or hundreds of millions of stem cells needed for a successful stem cell therapy.

What Does Stem Cell Therapy Cost?

Stem Cell Anti-Aging Treatments

Our Mesenchymal Stem Therapy Treatments have many anti-aging benefits. We are able to effect the whole body with a stem cells anti-aging IV Treatment or focus on specific areas like the face or hair. The stem cells target inflammation and then fix the route cause. Chronic inflammation always speeds up aging so this is the first way anti-aging stem cells effect.Next they donate mitochondria to weak cells. The mitochondria are like the engines of the cells and by having fresh, new mitochondria they have more energy and work better. The stem cells have also been found to extend telomere length in at least 6 types of cells. It is believed that research will show they do this for even more cells.The stem cell facial treatment is able to restore collagen and fat below the surface of the skin. This fills in the lines and restores a youthful appearance. It also improves skin quality and thickness.The Stem Cell Hair Restoration Treatment allows hair follicles that are closing to re-open. They also help regenerate the existing hair. stem cell therapy for anti-aging is wonderful

Type 2 Diabetes Stem Cell Treatment

Our Diabetes Stem Cell Treatment is extremely effective at mitigating the negative effects of Type 2 diabetes. The mesenchymal stem cell treatment for Type 2 diabetes is an IV of 300 Million mesenchymal stem cells. These stem cells send out cytokines that effectively reprogram the immune system to protect the pancreas instead of attacking it. This leads to stabilized blood glucose levels and proper insulin response. A proper diet with low sugar and low fast carbohydrates is needed to maintain results, but the stem cell treatment has a profound effect on Type 2 diabetes. Learn more about our Type 2 Diabetes Stem Cell Therapy.

Type 2 Diabetes Stem Cell Treatment Studies

.All of these studies back up how effective mesenchymal stem cells are at treating type 2 diabetes. Learn more about Dream Body Clinics Type 2 Diabetes Stem Cell Treatment Here.

Lyme Disease Stem Cell Treatment

Our Lyme Disease Stem Cell Treatment is extremely effective at mitigating the negative effects of Lyme disease. The mesenchymal stem cell treatment for Lyme disease is an IV of 300 Million mesenchymal stem cells. These stem cells send out cytokines that effectively reprogram the immune system to protect the body instead of attacking it. This leads to feeling normal again. Learn more about our Lyme Disease Stem Cell Treatment.

Human Growth Hormone - HGH Legal Fly & Buy Program

Our HGH Legal Fly & Buy Program is our longest running program that we have been doing for 8 years. It is legal to seek medical treatment abroad and return home with any prescribed medication. We start with a blood panel to make sure you are healthy and then prescribe the HGH to meet your country of origins law. For the USA that is 50 dose units and the rest of the world is a 90 day supply. We can legally send you home with up to 720 IU of pharmaceutical HGH like Norditropin HGH, Genotropin HGH or Humatrope HGH. That is enough for 2IU a day for a year. Learn more about our HGH Legal Fly & Buy Program.

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Our Genotropin HGH Legal Fly & Buy Program is the best. We can legally send you home with up to 720 IU of Genotropin HGH. Enough for 2IU a day for a year. Buy HGH the legal way. Learn more about our Genotropin HGH Legal Fly & Buy Program.

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Stem Cell Therapy Research

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Dream Body Clinic Stem Cell Therapy Stem Cells HGH

TORONTO -- Owen Snider was given as little as three months to live. His blood cancer had returned and the prognosis was not good. The news, delivered over the phone during the height of the early pandemic lockdown in spring 2020, was devastating.

The Ottawa-area retiree began putting his affairs in order, preparing for what appeared to be inevitable.

It was terrible, his wife Judith Snider told CTV News. But we finally decided that what we had to do was to live each day not to look forward to the end, but to look forward to tomorrow.

And yet, a year later, Snider is alive -- transformed, even -- and his non-Hodgkins lymphoma is in remission. His second chance is all thanks to a promising, Canadian-run program for cancer treatment called CAR T-cell therapy.

Snider became one of the first patients to participate in a national research program that is assessing whether this experimental treatment can be done safely in Canada and cheaper than in the U.S., where costs can run upwards of half a million dollars per patient.

I think I am a pretty successful lab rat, Snider, who previously endured chemotherapy treatments and a stem cell transplant, said in an interview.

Thirty days after treatment, the lymphoma was gone. So how can you not be happy about that?

CAR T-cell therapy is a type of gene therapy that trains or engineers a patients own immune system to recognize cancerous cells. A type of white blood cell, called a T-cell, is a key component of a bodys immune system. They are developed from stem cells in the bone marrow and help fight infection and disease by searching and targeting specific foreign substances, known as antigens, in the body.

The protein receptors on T cells bind to the protein antigens on the surfaces of foreign particles that fit those receptors, like a lock and key. The foreign substance is eradicated once their antigens are bound to a T-cell. But blood cancer cells are normal cells that undergo mutations, so they are not recognized as a foreign threat to the body. In other words, T-cells generally do not have the right receptor key to fit with the antigens of a cancer cell.

CAR T-cell therapy modifies the cells so they are able to identify the cancer cells and destroy them. Its a labour-intensive process that involves taking blood from a patient and separating the T-cells. Then scientists add a gene to the cells that gives them instructions to develop an artificial receptor called a chimeric antigen receptor, or CAR.

We actually take the T-cells out and we modify them in the lab and put them back into the patient. So now they're able to recognize the cancer and kill it off, explained Dr. Kevin Hay, Medical Director for Clinical Cell Therapy with BC Cancer.

I think we're just at the cusp of really understanding what this is going to do for patients in the future.

The therapy is a labour-intensive process -- Snider's cells were shipped to Victoria, B.C to be processed in a special lab facility, then shipped back to Ottawa about a week later, where they were infused back into his body.

The treatment is still being studied, but is already available for some cancers in the U.S. and Canada at a steep price.

Researchers began trials in Canada in 2019 to see if it could be done domestically at a lower cost, highlighting the importance of having key medical production and therapies available in Canada.

We knew we had to do domestic manufacturing and if we've learned anything from COVID-19, it's that domestic capability is really important when it comes to science and medicine, and this is a perfect example of that, said Dr. Natasha Kekre, a hematologist and lead researcher on the trail based at the Ottawa Hospital.

Progress was impacted slightly by the pandemic, but Snider was fortunate enough to participate and is the first patient to come forward to discuss their experience and why he hopes the program will expand across Canada to help others dealing with otherwise untreatable forms of cancer.

Scientists are hoping to release more data in the coming months -- more than 20 patients have been treated so far, according to Dr. Kekre.

This is hopefully just the beginning for us. So this first trial was a foundation to prove that we could actually manufacture T cells, that we could do this in a clinical trial. And so this trial will remain open for patients who are in need, she said.

So absolutely we feel like were opening a door.

Snider's first experience with cancer treatment was more than a decade ago, in 2010, when he underwent a powerful and aggressive chemotherapy regimen that helped him stay cancer-free for six years.

But the treatment was so harsh that when his cancer came back in 2016, doctors told him he could not go through that kind of chemotherapy again. Instead, Snider underwent a stem cell transplant, which gave him another four years without cancer, until April 2020.

This time the outlook was grim, so doctors decided to try and get him into the CAR T-cell trials that started just before the pandemic hit. The study was specifically for patients with acute lymphoblastic leukemia and non-Hodgkins lymphoma who were not responding to other treatments.

Snider said the entire process was a walk in the park compared to what he had gone through before. He was given a mild chemotherapy treatment for three days while his T-cells were being modified in a lab on the other side of the country.

[The T-cells] went to work right away. There's a period of time where there's a lot going on inside fighting each other and that sort of thing. You don't feel great or you don't really know how you feel, Snider described. The treatment was met with outstanding success.

And in 30 days, there was no lymphoma. I couldn't believe it.

For Dr. Kekre, the results bring hope. Snider has done quite well and does not have any evidence of lymphoma at the moment, she said.

I'm unfortunately in a business where I often have to give bad news, and it is really motivating and exciting to be able to offer therapies to patients who didn't have options and to make them better, she said.

The trial is currently at the stage where scientists are making sure the product remains safe. Side-effects can include neurotoxicity, which harms the nervous system, and cytokine release syndrome, which triggers an acute system-wide inflammatory response that can result in organs not functioning properly. But so far researchers have, for the most part, been able to manage and reverse any side effects.

With such promising outcomes for patients who otherwise had no options left, researchers are talking about expanding these studies across Canada and to other forms of cancer. For now, the lab in Victoria is the only facility equipped to make these cell modifications.

I think its really going to be revolutionary with how we treat cancer in the future, not just blood cancers, but all cancers, said Dr. Hay.

Today, Snider is healthy and strong, even able to chop wood at his home near Ottawa. He and his wife Judith, a retired federal judge, are enjoying life anew.

It certainly has given us a future that we didnt know we had, she said.

The treatment not only bought Snider extra time, but also significantly improved his quality of life.

What was given to me is practically a normal life, he added.

It's really just transformed, not just extended, but transformed my life.

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CAR T-cell therapy: Hear from a Canadian patient - CTV News

BlueSphere CEODr. David Apelian, M.D., Ph.D/Courtesy BlueSphere Bio

One of the greatest recent innovations in cancer treatment, CAR T therapies have sent some patients into long-lasting remission, with speedier recoveries, due to the lack of aggressive chemotherapy involved. They are the darling of numerous biopharma companies,including Sorrento Therapeutics, Kite Pharma (Gilead), and Allogene Therapeutics.

But they still have their limitations. They can only target a single tumor-associated antigen, recognize only cell surface antigens, and are not wholly tumor-specific, only targeting proteins expressed by normal and malignant cells. Enter BlueSphere Bio, a small biotech aiming to overcome these challenges with a precision approach to T cell therapy.

Headquartered in Pittsburgh, Pa.,and founded in 2018, BlueSphere has been operating under the radar. Not anymore. BioSpace sat down with Chief Executive Officer Dr. David Apelian, M.D., Ph.D., who shared why he believes the companys TCXpressis the premier T cell receptor platform that can have a significant impact on cancer.

When Apelian spoke with Co-Founder and Chief Scientific Officer Dr. Mark Shlomchik, M.D., Ph.D., about technologyhe was developing that could rapidly screen and capture thousands of T cell receptors from the sample more efficiently and cost-effectively than traditional methods, he was intrigued.

If you could identify those receptors that will direct the T cells to kill a tumor, amplify those cells in greater number outside the patient in a test tube, so to speak, and then reintroduce a healthy version of that T cell into the patient, youve essentially transcended what vaccines are hoping to do, said Apelian, who was previously chief medical officer at GlobeImmune, one of the early leaders in cancer vaccines. Youre getting right to the endpoint that you want.

The overall approach also consists of a downstream program that utilizes BlueSpheres NEOXpressplatform, which will enable the individualization of treatments for specific cell tumors.

BlueSphere profiles tumor cells by DNA and RNA sequencing and identifies the neoantigen profile in those tumors. In parallel, were extracting the T cells from that same tumor, were identifying the repertoire of TCRs, and then were marrying the two datasets up. Its a multiplex approach, Apelian said. Next, they will identify the ones that light up,characterize those T cell receptors and their ability to kill the tumor, and specifically recognize the target antigenbut not the native antigen.

BlueSphere will put the platform to its first test late in 2022 with the planned launch of a clinical trial in bone marrow recipients with high-risk leukemia. Apelian shared that acute myeloid leukemia (ALL) is likely to be the lead indication in that program. Here, they will be targeting minor histocompatibility antigens.

When a high-risk AML patient has not responded to first-line therapy or failed a first bone marrow transplant, Apelian said the chance of a successful transplant is probably 10%if that. While essentially a match, there are still many minor variations between a donor and recipient. This program aims to raise those odds.

We can engineer a T cell into the donor cell, which the recipient is already getting anyway; we can eliminate all the other minor antigen variants, and then shift that to a leukemia-only response, he explained. This enables complete engraftment, knocking out any residual leukemia cells along with the patients marrowand ultimately leading to improved long-term survival.

This is an example of an allogeneic, off-the-shelf target. On the other end of the spectrum, BlueSpheres technology enables it to take a preciseapproach to each patients tumor.

Apelian explained that certain cancers called hot tumorspossess a high number of different antigens. Melanoma probably has the most complex neoantigen profilebecause these tumors are caused by exposure to the sun, which allows more mutations to occur. Non-small-cell lung cancers also have a fair number of neoantigens.

We can literally take a patients tumor and extract the tumor-specific antigens that patient has generated uniquely in their own tumor, and then identify the receptors to target the patients very own tumors, Apelian said.

The benefit of this individualized therapy, he continued, is that the patients body is already making those T cell receptors, so its very unlikely were going to make a receptor thats going to be toxic to the patient.

Then, BlueSphere can enrich these receptors, grow them in large quantities in a re-engineered healthy version of the T cell, and replace them in the patients body.

Those T cells are sick;theyre exhausted. So, were taking that receptor part and re-engineering it into a healthy version of their own T cell, and then reintroducing it into the patient, Apelian said. Thats going to be the game-changer for solid tumors.

Conversely, there are other cancers known as cold tumors. These include ovarian cancer, prostate cancer, pancreatic cancer, glioblastomas, and most breast cancers. Apelian believes his companys platform has the throughput capability to tackle these as well.

We think we have enough throughput with our TCXpressto even identify TCRs for those neoantigens in so-called cold tumors, but thats kind of a downstream project for us, he said.

In the middle of this range, BlueSphere will look at other exciting targets for solid tumors that can be re-engineered ahead of time to treat a myriad of different cancers.

While some elements of the work will be off-the-shelf, and there is a movement in the industry toward finding a universal cell, Apelian explainedmany advantages to the autologous approach.

I understand the motivation for that [quest for a universal cell], but I think youre going to lose a lot of the specificity and the elegancethe exquisite specificity of T cell, he said. We think its going to be more likely that autologous approaches and individualized therapies will be safer and more effective.

BlueSphere is conducting what it calls the virtual patient program to determine the next steps in its pipeline. Instead of waiting to completemanufacturing aspects necessary for individualized tumor therapies, the company is building a tissue repository to test various tumors. Here, they will identify the neoantigen profile, extract the T cell repertoire from the tumor, and characterize the potential to recognize and kill the tumor.

Were collecting tissues, local tissues and some tissues from the National Cancer Institute, and were testing as if they were patients in a study, Apelian explained.

He also expressed an interest in working collaboratively to solve cancers outside of BlueSpheres purview and other diseases. I could see this [technology] being useful a huge array of diseases that we can treat by appropriately re-engineering T cells to have the right T cell receptors, he said.

With obvious ambition and belief in its platform, BlueSphere expects to double its workforce, which sits at 38 people, over the next 18 to 24 months.

Its a super exciting time for the company, Apelian said, It feels like moonshot startup excitement, which is fun. Everyone kind of appreciates how game-changing this platform could be.

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New Precision Platform Could Be Cell Therapy Game-Changer - BioSpace

PlateletBio, a company developing a new class of cell therapies based on the biology of platelets, has raised $75.5 million to advance its drug pipeline, including a lead candidate for a rare bleeding disorder on track to reach the clinic next year.

Platelets are components of blood best known for their role forming clots that stop bleeding. But Watertown, Massachusetts-based PlateletBio notes that platelets have other properties, including a role delivering growth factors and proteins throughout the body. PlateletBio is developing therapies that take advantage of these properties, but rather than using platelets from a patient or healthy donors, the startup makes them.

In the body, platelets are formed in bone marrow. PlateletBio produces its platelet-like cells, or PLCs, inside a bioreactor that mimics bone marrow conditions. The source material for its PLCs are stem cells, which have the ability to become almost any cell or tissue in the body.

Platelets are technically not cells. They dont have a nucleus, but thats an advantage for therapeutic applications. Since a PlateletBio therapy wont introduce DNA into a patients body, the potential risks that come from introducing foreign genetic material are avoided. PlateletBio says it can produce PLCs with new features and therapeutic payloads that include antibodies, signaling proteins, therapeutic proteins, and nucleic acids.

PlateletBios lead cell therapy candidate is being developed to treat immune thrombocytopenia, a blood disorder in which the immune system mistakenly sees a patients platelets as foreign and destroys them. Immune thrombocytopenia patients have dangerously low platelet counts that make them susceptible to bleeding.

There is no FDA-approved treatment for the underlying cause of immune thrombocytopenia, but corticosteroids are used to try to dampen the immune systems attack on platelets. Platelet transfusions are another option, but the National Organization for Rare Disorders notes that these treatments are usually reserved for emergencies because the platelets are likely to be destroyed by antibodies produced by the patient.

Patients who have not responded to earlier treatments have two FDA-approved small molecule options: Tavalisse, from Rigel Pharmaceuticals, and the Swedish Orphan Biovitrum drug Doptelet. Sanofi aims to treat the disease with a small molecule called rilzabrutinib. That drug is designed to block Brutons tyrosine kinase, a protein that plays a role in the development of a B cells, a type of immune cell. Sanofi acquired the molecule last year via its $3.7 billion acquisition of Principia Biopharma.

The lead disease target for the Principia drug was multiple sclerosis. In September, Sanofi reported that rilzabrutinib failed that Phase 3 study. A separate Phase 3 test in immune thrombocytopenia is ongoing, as is a mid-stage clinical trial in another autoimmune condition called IgG4-related disease.

PlateletBio isnt the only company trying to turn a component of the blood into a new type of cell therapy. Cambridge, Massachusetts-based Rubius Therapeutics is developing cell therapies based on red blood cells. After disappointing early clinical trial results in the rare disease phenylketonuria last year, Rubius shifted its focus to cancer and immune system disorders. PlateletBios PLCs would represent an entirely new approach to treating immune thrombocytopenia. According to PlateletBios website, the company plans to file an investigational new drug application for its therapeutic candidate in the first half of next year.

PlateletBio is based on the research of Harvard University scientist Joseph Italiano, who co-founded the company under the name Platelet BioGenesis. When the startup emerged in 2017, it was developing platelets that could address the platelet shortage problem facing blood donation centers. Two years ago, the startup expanded its Series A round with $26 million in additional financing and plans to make its platelets into cell therapies. Besides immune thrombocytopenia, other diseases the biotech aims to treat include osteoarthritis and liver fibrosis.

PlateletBios latest financing, a Series B round, adds new investors SymBiosis, K2 HealthVentures, and Oxford Finance. Earlier investors Ziff Capital Partners and Qiming Venture Partners also participated in the new round.

This is a major milestone for PlateletBio, adding capital and resources needed to advance our innovative platelet-like cell therapy science and manufacturing platform and support key corporate initiatives over the next 18 to 24 months, Sam Rasty, the startups president and CEO, said in a prepared statement.

Photo by Flickr user Marco Verch via a Creative Commons license

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Cell therapy biotech PlateletBio reels in $75M as it looks ahead to first clinical test - MedCity News

SAN DIEGO, Nov. 02, 2021 (GLOBE NEWSWIRE) -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, today announced the establishment of its Cell Therapy Scientific Advisory Board (SAB). The Cell Therapy SAB is comprised of industry and academic leaders in the cell therapy field, covering important areas of expertise including cutting edge research, preclinical development, manufacturing, and clinical development.

The Cell Therapy SAB will play an important role in advising and guiding the companys efforts to develop safe and effective cell therapies targeting receptor-tyrosine kinase-like Orphan Receptor 1 (ROR1), leveraging our deep expertise on ROR1 and the single chain variable fragment (scFv) of our ROR1 antibodies, including cirmtuzumab. ROR1 is highly expressed by many solid tumors as well as hematological malignancies and confers both an aggressive phenotype and survival advantage to the tumor cells. Cirmtuzumab binding to ROR1 on leukemia and lymphoma cells decreases tumor cell proliferation and survival by blocking Wnt5a-induced activation, while it does not bind to normal adult tissues. Cirmtuzumab has also demonstrated encouraging safety and efficacy results in its ongoing Phase 1/2 study in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) as well as in a Phase 1b study in combination with paclitaxel for the treatment of patients with Her2-negative breast cancer.

We are pleased to welcome our newly appointed scientific advisors, whose deep expertise in cell therapy research and development will help us bring safe and effective ROR1 targeted cell therapies to patients faster, said James Breitmeyer, M.D., Ph.D., Oncternals President and CEO. We believe that ROR1 is an ideal target for next generation cell therapies due to its proven role in tumor progression and its wide expression in many cancer types with significant unmet needs.

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The members of the Oncternal Cell Therapy SAB include:

Michael Wang, MD, Endowed Professor in the department of Lymphoma & Myeloma at MD AndersonDr. Wang has published more than 200 peer-reviewed papers and has presented his work at meetings nationally and internationally. He is the Director of the Mantle Cell Lymphoma (MCL) Program of Excellence and Co-Director of the B-Cell Lymphoma Moon Shot Program at the University of Texas MD Anderson Cancer Center. The Wang Laboratory at MD Anderson research program aims to elucidate the mechanisms underlying therapeutic resistance in B-cell lymphoma and to translate these findings to the clinic to improve patient outcomes. Dr. Wang obtained his M.D. from Shandong Medical University and M.S. from Beijing University Medical School, and completed his clinical training as a resident at Norwalk Hospital, Norwalk, Conn., and as a Fellow in Oncology and in Hematology at MD Anderson.

Angela Shen, MD, MBA, Clinical and Translational Market Sector Leader Mass General BrighamDr. Shen has unique, deep knowledge of the cell and gene therapy landscape having provided clinical, regulatory, and strategic leadership for autologous and allogeneic CAR-T cell therapies, NK cell therapies, and other novel cell therapy programs across industry. Dr. Shen currently hold a position at Mass General Brigham (formerly known as Partners HealthCare), an affiliate of Harvard Medical School and serves a part-time CMO at Walking Fish Therapeutics, Inc. Previously, she held Chief Medical Officer (CMO) positions at multiple biotech companies, including Arcellx, NKarta, Arvinas, and acting CMO of Tizona. Dr. Shen led the clinical team at Novartis responsible for designing and launching the industrys first multi-site, registration CAR-T cell therapy trial supporting the approval of Kymriah (CTL019, CART-19). She received a BS through Rensselaers accelerated biomedical program, and holds an MD from Albany Medical College in New York and MBA from New York University Stern School of Business.

Marcela V. Maus, MD, PhD, Associate Professor, Medicine, Harvard Medical School, Director of Cellular Immunotherapy, Cancer Center, Massachusetts General HospitalDr. Maus is a translational physician-scientist in the field of cancer immunology. Her laboratory focuses on the design, generation, and use of innovative forms of immune cell engineering, including chimeric antigen receptors and investigates basic mechanisms of human immunology to design and test novel immune-based therapeutic interventions in vitro, in mouse models, and in patients. Dr. Maus received her S.B. from the Massachusetts Institute of Technology, and her M.D. and Ph.D. degrees from the University of Pennsylvania. Dr. Maus trained in internal medicine at University of Pennsylvania and in hematology and medical oncology at Memorial Sloan Kettering, and is board-certified in these three disciplines. Her laboratory research training was focused on gene and cell therapies, and occurred in the laboratories of Dr. Katherine High, Dr. Michel Sadelain, and Dr. Carl June.

Sadik Kassim, PhD, Chief Technology Officer at Vor BiopharmaDr. Kassim is a cell and gene therapy bioprocessing and translational research expert. Dr. Kassim served as Executive Director at Kite Pharma where he led the development of manufacturing processes for autologous CAR-T and TCR-based cell therapies. He and his team at Kite led the BLA and MAA filing efforts for Kites X-19 product, which is a CD19 CAR-T therapy for Mantle Cell Lymphoma. Before Kite, Dr. Kassim served as Chief Scientific Officer at Mustang Bio, where he was the first employee and oversaw the foundational build-out of the companys preclinical and manufacturing activities. Earlier in his career, Dr. Kassim was Head of Early Analytical Development for Novartis Cell and Gene Therapies Unit, where he and his team contributed to the BLA and MAA filings for Kymriah. Dr. Kassim earned his BS in cell and molecular biology from Tulane University and received his PhD in microbiology and immunology from Louisiana State University. After receiving his PhD, he was a research fellow in the lab of Dr. James Wilson at the University of Pennsylvanias Gene Therapy Program.

About Oncternal Therapeutics

Oncternal Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies for the treatment of cancers with critical unmet medical need. Oncternal focuses drug development on promising yet untapped biological pathways implicated in cancer generation or progression. The clinical pipeline includes cirmtuzumab, an investigational monoclonal antibody designed to inhibit the ROR1 pathway, a type I tyrosine kinase-like orphan receptor, that is being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) and in an investigator-sponsored, Phase 1b clinical trial in combination with paclitaxel for the treatment of women with HER2-negative metastatic or locally advanced, unresectable breast cancer, as well as a Phase 2 clinical trial of cirmtuzumab in combination with venetoclax, a Bcl-2 inhibitor, in patients with relapsed/refractory CLL. Oncternal is also developing a chimeric antigen receptor T cell (CAR-T) therapy that targets ROR1, which is currently in preclinical development as a potential treatment for hematologic cancers and solid tumors. The clinical pipeline also includes TK216, an investigational targeted small-molecule inhibitor of the ETS family of oncoproteins, that is being evaluated in a Phase 1/2 clinical trial for patients with Ewing sarcoma alone and in combination with vincristine chemotherapy. More information is available at https://oncternal.com.

Contact Information:

InvestorsRichard VincentChief Financial Officer858-434-1113rvincent@oncternal.com

MediaCorey DavisLifeSci Advisors212-915-2577cdavis@lifesciadvisors.com

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Oncternal Therapeutics Announces Formation of Cell Therapy Scientific Advisory Board - Yahoo Finance