Category Archives: Cell Therapy

The main conditions treated by stem cell injections include knee osteoarthritis, cartilage degeneration, and various acute conditions, such as a torn ACL, MCL, or meniscus. Stem cell therapy may speed healing times in the latter, while it can actually rebuild tissue in degenerative conditions such as the former.

Thats a major breakthrough. Since cartilage does not regenerate, humans only have as much as they are born with. Once years of physical activity have worn it away from joints, there is no replacing it. Or at least, there wasnt before stem cell therapy.

Now, this cutting-edge technology enables physicians to introduce stem cells to the body. Thesemaster cells are capable of turning into formerly finite cell types to help the body rebuild and restore itself.

Although it may sound like an intensive procedure, stem cell therapy is relatively straightforward and usually minimally invasive. These days, physicians have many rich sources of adult stem cells, which they can harvest right from the patients own body. This obviates the need for embryonic stem cells, and thereby the need for moral arguments of yore.

Mesenchymal stem cells (MSCs) are one of the main types used by physicians in treating knee joint problems. These cells live in bone marrow, butincreasing evidence shows they also exist in a range of other types of tissue.This means they can be found in places like fat and muscle. With a local anesthetic to control discomfort, doctors can draw a sample of tissue from the chosen site of the body. The patient usually doesnt feel pain even after the procedure. In some cases, the physician may choose to put the patient under mild anesthesia.

They then isolate the mesenchymal stem cells. Once they have great enough numbers, physicians use them to prepare stem cell injections. They insert a needle into the tissue of the knee and deliver the stem cells back into the area. This is where they will get to work rebuilding the damaged tissue. Although the mechanisms arent entirely clear, once inserted into a particular environment, mesenchymal stem cells exert positive therapeutics effectsinto the local tissue environment.

Mechanisms of action of mesenchymal stem cells appear to include reducing inflammation, reducing scarring (fibrosis), and positively impacting immune system function.

Thats not quite enough to ensure a successful procedure, however. Thats why stem cell clinics may also introduce growth factors to the area. These are hormones that tell the body to deliver blood, oxygen,and nutrients to the area, helping the stem cells thrive and the body repair itself.

Physicians extract these growth factors from blood in the form of platelet-rich plasma (PRP). They take a blood sample, put it in a centrifuge and isolate the plasma, a clear liquid free of red blood cells, but rich in hormones needed for tissue repair.

So, what can a patient reasonably expect when it comes to stem cell therapy, in terms of time and cost outlay?

The answers to both of these questions differ depending on the clinic doing the procedure and the patients level of knee degradation. Some clinics recommend a course of injections over time. Meanwhile, others prepare the injection and deliver it back to the patient in only a matter of hours. Either way, the treatment is minimally invasive, with fast healing times and a speedy return to normal (and even high-intensity) activity.

Some quotes for stem cell knee treatment are as low as $5,000. Others cost up to $20,000 or more. Again, this depends on how many treatments a patient needs, as well as how many joints theyre treating at the same time. Because its easier to batch prepare stem cells, a patient treating more than one knee (or another joint) can address multiple sites for far less. The procedure would only cost an addition of about $2,000 or so per joint.

No treatment proves effective every time. However, insofar as patients reporting good results for stem cell injections, the overall evidence does lean in a beneficial direction.Studies at the Mayo Clinic, for instance, indicate that while further research is needed, it is a good option for arthritis in the knee. Anecdotal reports are positive as well. Patients report it as an effective alternative to much more invasive solutions, such as arthroscopic or knee replacement surgery.

Other studies point to the need for caution. Stem cell therapy and regenerative medicine, in general, are only now exiting their infancies. There arent enough high-quality sources from which to draw at this point, so hard and fast conclusions remain elusive. Of the studies that do exist, some contain unacceptably high levels of bias.

Of course, any new treatment will face these kinds of challenges in the beginning. For those who need an answer to knee pain, and havent yet found one that works, its likely worth the risk that it wont prove as effective as they hoped. But what about other risks?

The good news about this form of stem cell therapy is that the patient uses their own cells. That means they completely skip over the dangers that accompany donor cells. The main one of which is graft-versus-host disease (in which the donor cells initiate an immune response against the patients body). Because the cells have all the same antibodies, neither the body nor the reintroduced cells will reject one another.

Also, the relatively low-stakes outpatient nature of the procedure (versus, say, a bone marrow transplant) means that the chances of something going wrong are much reduced.

However, there do exist some risks wherever needles come into play. It is possible to get an infection at the site of the blood draw as well as at the injection site, but these risks are quite low. Other risks include discoloration at theinjection site or soreness. While some people fear the possible growth of stem cells at the site of injection into a tumor, it is unlikely for this to happen, because physicians utilize adult stem cells for these procedures that have a low proliferative capacity.

These adult stem cells tend to be much safe than pluripotent stem cell types. Examples of pluripotent stem cells are embryonic stem cells (derived from embryos) and a type of lab-made stem cell known as induced pluripotent stem cell (iPS cell).

For those who think stem cell therapy could prove beneficial, its time to set up a consultation with your doctor. Multiple factors will influence whether or not its a good idea. These include age, health, andseverity of the condition and other available treatments. However, overall, this form of regenerative medicine is reasonably affordable, very low-risk, and typically effective.

Are you seeking a stem cell treatment for your knees or other joints?To support you,we have partnered withOkyanosa state-of-the-art facility providing patients with advanced stem cell treatments.

The group offers treatments for arange of chronic conditions, includingosteoarthritis and degenerative joint disease, which are leading causes of knee pain.

If you are seeking a stem cell treatment for knee pain or other chronic condition,contact Okyanos for a Free Medical Consultation.

What questions do you still have about stem cell therapy for knees? Ask them below and we will get you answers.

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Stem Cell Therapy For Knees | What You Need To Know ...

Cambridge Healthtech Institutes 5th AnnualAugust 30-31, 2018

In 2017, two CAR T cell therapies were approved by the Food and Drug Administration (FDA). With multiple engineered receptors making preclinical impact, many biotech and pharma companies are already entering other clinical trials in a race to get to market. Has this promising field finally reached a tipping point? Technical considerations and translational challenges relating to cell therapy development, manufacturing practicability, clinical trial approaches, cell quality and persistence, and patient management remain. Cambridge Healthtech Institutes 5th Annual Adoptive T Cell Therapy 2: Development conference focuses on the steps needed to deliver CAR, TCR, NK, and TIL therapies to the clinic. Overall, this event addresses clinical progress, case studies, and the critical components for making adoptive T cell therapy work.

Final Agenda

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THURSDAY, August 30

7:45 am Registration & Morning Coffee (Harbor Level)

8:25 Chairpersons Opening Remarks

Amy Hines, BSN, RN, Director, Collection Network Management, Be The Match BioTherapies

8:30 FEATURED PRESENTATION: A Translational Perspective of Development of Yescarta (Axicabtagene Ciloleucel), a First-in-Class CAR T Cell Product for Diffuse Large B Cell Lymphoma

Adrian Bot, MD, PhD, Vice President, Translational Sciences, Kite, a Gilead Company

Yescarta (Axicabtagene Ciloleucel) is an anti-CD19 CAR T cell therapy that received approval for treatment of relapsing or refractory DLBCL. This presentation describes key elements of the translational program, correlates of toxicities and durable objective response, product characteristics, patient conditioning, and importance of tumor microenvironment. It also showcases major lessons learned and challenges in developing cell-based immunotherapies.

9:00 NEW: Selected Poster Presentation: TAC-T, A Novel T Cell Therapy, Co-Opts the Endogenous T Cell Receptor for Effective, Safe, and Persistent Tumor Rejection

Christopher W. Helsen, PhD, Director, R&D and Head, Platform Development, Triumvira Immunologics, Inc.

9:30 Predictors of Response to CD19-Specific CAR T Therapy in B-CLL

Jun Xu, PhD, Associate Director, Product Development Laboratory, Center for Advanced Cellular Therapeutics, Perelman Center for Advanced Medicine, University of Pennsylvania

To date, it has not been possible to identify patient- or disease-specific factors that predict why some B-CLL patients and not others have such dramatic responses to CAR T cell treatment. We explored the mechanisms associated with clinical response and lack of response to CAR T therapy, providing evidence for intrinsic T cell fitness in mediating durable anti-tumor responses and long-term complete remissions.

10:00 Coffee Break in the Exhibit Hall (Last Chance for Poster Viewing) (Commonwealth Hall)

10:45 Facing the Challenges of Apheresis Network Management

Amy Hines, BSN, RN, Director, Collection Network Management, Be The Match BioTherapies

For companies working in cell therapies, managing and maintaining your apheresis (cell collection) network is a critical challenge. How do you know which center is best equipped to handle your needs? How do you evaluate their compliance with FDA and international regulations? Hines discusses the key questions to ask and gives you the tools youll need to evaluate centers, secure your supply chain and advance your cell therapy program.

11:15 Solving the Challenges of Large-Scale GMP T Cell Manufacturing

Steven L. Highfill, PhD, Assistant Director, Product Development and Management, Center for Cellular Engineering, Clinical Center, National Institutes of Health

This presentation covers current, ongoing GMP manufacturing efforts at the NIH. Highlights focus on CAR T cell manufacturing and some of the challenges that we had to overcome specifically when using autologous patient-derived starting material. In addition, I discuss some newer closed-system manufacturing platforms that will make it easier for academic institutes to provide cell therapy options to their patients.

11:45 Sponsored Presentation (Opportunity Available)

12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Session Break

1:40 Chairpersons Remarks

Adrian Bot, MD, PhD, Vice President, Translational Sciences, Kite, a Gilead Company

1:45 FEATURED PRESENTATION: Stress-Resistant T Cell Therapy for Solid Tumors

Prasad S. Adusumilli, MD, FACS, FCCP, Associate Attending and Deputy Chief, Thoracic Surgery; Head, Solid Tumors Cell Therapy, Cellular Therapeutics Center; Director, Mesothelioma Program, Memorial Sloan Kettering Cancer Center

CAR T cell therapy efficacy in solid tumors is limited by PD-1/PD-L1 pathway. We have shown that exhausted CAR T cells can be rescued by anti-PD1 agents or by a decoy receptor, PD-1 dominant negative receptor cotransduced with CAR T cells to promote functional persistence. The presentation focuses on cell-intrinsic and extrinsic methods in overcoming checkpoint blockade in cellular immunotherapy.

2:15 TRAP CAR T & Related Cell Therapies: Can Local Delivery Solve Efficacy and Safety Challenges in Solid Tumor Immuno-Oncology?

Janet R. Rea, MSPH, RAC, Senior Vice President, Regulatory, Quality & Clinical Affairs, Atossa Genetics

This presentation reviews cell therapy evolution and challenges. It includes considerations of local delivery options using breast cancer as a model.

2:45 Selected Poster Presentation: Phase I Study of an Adoptive Cellular Immunotherapy by Silencing cbl-b in Autologous Peripheral Blood Mononuclear Cells

Kathrin Thell, PhD, MSc, In Vivo Scientist, Apeiron Biologics AG

3:15 Refreshment Break (Commonwealth Hall)

3:45 Eutilexs 4-1BB CTL Adoptive T Cell Therapy: Clinically Safe and First Efficacy in Solid Tumors

Agustin de la Calle, PhD, CBO, Eutilex Co., Ltd.

Eutilexs 4-1BB CTL therapy is the autologous T cell therapy proven safe in man without treatment-related toxicity and no CRS. Efficacy in hematological cancers and solid tumors: brain, breast, lung, tracheal, pancreatic cancers, CRC and melanoma. Complete remissions were observed in Hodgkins and NK/T cell lymphomas. Phase I safety accepted single dose in terminal patients but relapsed patients became responsive again to further treatments. Leader in COGS: simple outpatient procedure.

4:15 Engineering NK Cells for Enhanced Potency and Persistence

James B. Trager, PhD, Senior Vice President, R&D, Nkarta, Inc.

NK cells form a first line of defense against cancer, and they can be formidable mediators of cytotoxicity and adaptive immunity. Efforts to maximize their potential as cancer therapeutics are hampered by difficulty in expanding NK cells, relatively short in vivo persistence, and the ability of tumor cells to evade NK recognition. We discuss recent progress in overcoming these barriers to successful therapeutic application of NK cells.

4:45 FEATURED PRESENTATION: Tricked-Out CARs: Next-Generation Approaches to Enhance and Optimize CAR T Cell Function

Benjamin Boyerinas, PhD, Senior Scientist, Immunotherapy, bluebird bio

Genetically engineered CAR T cells can be further engineered to survive and overcome immune evasion mechanisms employed by tumors. We have been developing a novel TGF- signal conversion platform that provides a T cell supportive signal upon exposure to TGF- within the hostile tumor microenvironment. This approach, combined with other methodologies such as gene editing and drug-regulated activation, have the potential to enhance specific activity within solid tumors.

5:15 End of Day

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FRIDAY, August 31

7:45 am Registration (Plaza Level)

8:00 Breakout Discussion Groups with Continental Breakfast (Beacon Hill)

This session features discussion groups that are led by a moderator who ensures focused conversations around the key issues listed. Attendees choose to join a specific group, and the small, informal setting facilitates sharing of ideas and active networking. Details on the topics and moderators are available on the conference website.

9:00 Chairpersons Remarks

Paul Rennert, PhD, President & CSO, Aleta Biotherapeutics, Inc.

9:05 GOLD: Activation-Induced Payload Delivery for T Cell Therapies

Gus Zeiner, PhD, CSO, Chimera Bioengineering

GOLD is an endogenous post-transcriptional gene regulatory node that couples T cell metabolic states to transgenic payload outputs. Conditional payload expression is induced by signaling through either the native T cell receptor or a CAR. GOLD is payload-agnostic, and enforces low basal payload expression in resting T cells with a wide dynamic range in activated T cells. GOLD-mediated regulation is non-immunogenic, making GOLD-enabled T cell therapeutics compatible with long-term persistence.

9:35 Developing Tumor Infiltrating Lymphocytes for the Treatment of Cancer

Maria Fardis, PhD, President & CEO, Iovance Biotherapeutics

Recent FDA approvals of Kymriah and Yescarta show that cell therapies are viable options for treatment of hematological malignancies. Incidence of solid tumors are, however, approximately 10 times higher than hematological malignancies. Available therapies for solid tumors include chemotherapy, radiotherapy, and immunotherapy. Immunotherapies, such as Anti-PD-1 antibodies, have shown promise, but in many cases, although the overall response rate is not high, discontinuation due to adverse events remains an issue. Iovance is developing -infiltrating lymphocytes (TIL), a one-time cell therapy treatment that leverages and enhances the bodys natural defenses against certain aggressive solid tumors. TIL is currently under investigation in several multi-center Phase II clinical trials and preliminary results have demonstrated safety and efficacy in melanoma, head and neck and cervical cancer patients with multiple prior therapies which constitutes unmet medical need.

10:05 PM21-NK Cells for Cancer Therapy

Robert Igarashi, PhD, President, CytoSen Therapeutics

CytoSen is advancing NK cell therapy for treatment of cancer. CytoSens methods for stimulating NK cells with membrane bound (IL21), originally developed by Dr. Dean A. Lee, produces NK cells with high anti-tumor potency and can generate the highest doses. We plan to leverage our particle-based platform, that has logistical advantages, to pursue clinical studies in leukemia.

10:35 Coffee Break (Plaza Level)

11:00 A TCR-Based Chimeric Antigen Receptor

Even Walseng, PhD, Staff Scientist, Experimental Immunology Branch, National Cancer Institute, National Institutes of Health; Department of Immunology, Hospital Radiumhospitalet, Institute for Cancer Research, University of Oslo

Although CARs are very potent, the recognition is limited to membrane antigens which represent around 1% of the total proteins expressed, whereas TCRs have the advantage of targeting any peptide resulting from cellular protein degradation. To expand the horizon of TCR use, we have successfully fused a soluble TCR construct to a CAR-signaling tail. We demonstrate that the TCR-CAR redirection is not restricted to T cells and hence opens therapeutic avenues combing the killing efficiency of NK cells with the diversified target recognition of TCRs.

11:30 Hijacking CAR19 T Cells to Address Critical Issues in Cell Therapy: Application to Diverse Indications

Paul Rennert, PhD, President & CSO, Aleta Biotherapeutics, Inc.

The Aleta platform addresses critical issues in cell therapy including CAR persistence, antigen escape and antigen heterogeneity, and provides important solutions for treating both hematologic and solid tumors. The key element of our technology is the use of novel fusion proteins to redirect CAR T specificity. Our lead programs are directed to B cell malignancies, AML and solid tumors.

12:00 Close of Adoptive T Cell Therapy 2: Development

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Adoptive T Cell Therapy 2: Development

Gene therapy is a field of biomedical research with the goal of influencing the course of various genetic and acquired (so-called multi factorial) diseases at the DNA/RNA level. Cell therapy aims at targeting various diseases at the cellular level, i.e. by restoring a certain cell population or using cells as carriers of therapeutic cargo. For many diseases, gene and cell therapy are applied in combination. In addition, these two fields have helped provide reagents, concepts, and techniques that are illuminating the finer points of gene regulation, stem cell lineage, cell-cell interactions, feedback loops, amplification loops, regenerative capacity, and remodeling.

Gene therapy is defined as a set of strategies that modify the expression of an individuals genes or repair abnormal genes. Each strategy involves the administration of a specific nucleic acid (DNA or RNA). Nucleic acids are normally not taken up by cells, thus special carriers, so-called 'vectors' are required. Vectors can be of either viral or non-viral nature.

Cell therapy is defined as the administration of living whole cells for the patient for the treatment of a disease. The origin of the cells can be from the same individual (autologous source) or from another individual (allogeneic source). Cells can be derived from stem cells, such as bone marrow or induced pluripotent stem cells (iPSCs), reprogrammed from skin fibroblasts or adipocytes. Stem cells are applied in the context of bone marrow transplantation directly. Other strategies involve the application of more or less mature cells, differentiated in vitro (in a dish) from stem cells.

Historically, the discovery of recombinant DNA technology in the 1970s provided the tools to efficiently develop gene therapy. Scientists used these techniques to readily manipulate bacterial and viral genomes, isolate genes, identify mutations involved in human diseases, characterize and regulate gene expression and produce human proteins from genes (e.g. production of insulin in bacteria revolutionized medicine). Later, various viral and non-viral vectors were developed along with the development of regulatory elements (e.g. promoters that regulate gene expression), which are necessary to induce and control gene expression. Gene transfer in animal models of disease have been attempted and led to early success. Various routes of administrations have been explored (injection into the bloodstream, into the ventricles of the brain, into muscle etc).

The development of suitable gene therapy treatments for many genetic diseases and some acquired diseases has encountered many challenges, such as immune response against the vector or the inserted gene. Current vectors are considered very safe and recent gene therapy trials documented excellent safety profile of modern gene therapy products. Further development involves uncovering basic scientific knowledge of the affected tissues, cells, and genes, as well as redesigning vectors, formulations, and regulatory cassettes for the genes. While effective long-term treatments for many genetic and inherited diseases are elusive today, some success is being observed in the treatment of several types of immunodeficiency diseases, cancers, and eye disorders.

Historically, blood transfusions were the first type of cell therapy and are now considered routine. Bone marrow transplantation has also become a well-established medical treatment for many diseases, including cancer, immune deficiency and others. Cell therapy is expanding its repertoire of cell types for administration. Cell therapy treatment strategies include: isolation and transfer of specific stem cell populations, induction of mature cells to become pluripotent cells, administration of effector cells and reprogramming of mature cells into iPSCs. Administration of large numbers of effector cells has benefited cancer patients, transplant patients with unresolved infections, and patients with vision problems.

Several diseases benefit most from treatments that combine the technologies of gene and cell therapy. For example, some patients have a severe combined immunodeficiency disease (SCID) but unfortunately, do not have a suitable donor of bone marrow. Scientists have identified that patients with SCID are deficient in adenosine deaminase gene (ADA-SCID), or the common gamma chain located on the X chromosome (X-linked SCID). Several dozen patients have been treated with a combined gene and cell therapy approach. Each individuals hematopoietic stem cells were treated with a viral vector that expressed a copy of the relevant normal gene. After selection and expansion, these corrected stem cells were returned to the patients. Many patients improved and required less exogenous enzymes. However, some serious adverse events did occur and their incidence is prompting development of theoretically safer vectors and protocols. The combined approach also is pursued in several cancer therapies.

Genome editing (gene editing) has recently gained significant attention, due to the discovery and application of the clustered regularly interspaced short palindromic repeats (CRISPR) system. Actually, genome editing dates back several years and earlier generation genome editing systems are currently tested in clinical trials (such as zinc-finger nucleases). The aim of genome editing is to disrupt a disease-causing mutation or correct faulty genes at the chromosomal DNA. Genome editing can be performed in the patients own cells in vitro and edited cells can be administered to the patient (thus genome editing can be combined with cell therapy). However, it is also possible to perform genome editing in vivo by administering the genome editing agent packaged in viral and non-viral vectors.

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Gene & Cell Therapy Defined | ASGCT - American Society of ...

Through the PRIME-XV media platform, and a range of complementary products designed to work seamlessly alongside it, we offer advanced cell culture media solutions for stem and primary cells to support basic, translational, and clinical research, as well as commercial applications.

Featuring chemically-defined, xeno-free, and serum-free, formulations, the platform is precisely developed and rigorously tested to ensure the consistent delivery of sufficient cell populations with the desired functionality and phenotype for therapeutic applications.

Designed to support cutting-edge therapies at every stage of development, the platform is cGMP manufactured using raw ingredients from a strictly controlled supply chain to minimize risk from adventitious agents and features document packets to facilitate the regulatory submission process.

Since cell therapies frequently require individualized support, we also offer process optimization for media and protocols, as well as custom manufacturing and packaging at any scalefrom 10-10,000 L (liquid), or 1-7000 kg (dry powder).

With more than four decades of experience supporting commercial biotherapeutics, we have cultivated deep industry insight, cell culture media expertise, and a legacy of unrivaled customer servicepositioning us as the cell culture media partner of choice to support your cell therapy needs.

We know the emerging cell therapy industrys needs are nuanced. If you dont see the product or service that fits your needs, or you have questions and would like individualized support, we are here to help. Contact us today to speak with a media specialist.

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Cell Therapy | Irvine Scientific

Cellular therapy (CT) is the transplantation of human cells to replace or repair damaged tissue and/or cells. With new technologies, innovative products, and limitless imagination, many different types of cells may be used as part of a therapy or treatment for a variety of diseases and conditions. Some of the cells that may be used include hematopoietic (blood-forming) stem cells (HSC), skeletal muscle stem cells, mesenchymal stem cells, lymphocytes, dendritic cells, and pancreatic islet cells.

While the research is evolving, various cell types will be developed into treatments as novel cell therapies and studied for potential applications. Hematopoietic stem cell transplantation (also called bone marrow transplant) is the most frequently used cell therapy and is used to treat a variety of blood cancers and hematologic conditions. Potential applications of cell therapies include treating cancers, autoimmune disease, urinary problems, and infectious disease, rebuilding damaged cartilage in joints, repairing spinal cord injuries, improving a weakened immune system, and helping patients with neurological disorders.

Regenerative Medicine

Hematopoietic Stem Cells

Hematopoietic Stem Cells for Donation

How are Stem Cells Regulated?

The Role of Standards and Accreditation

Considerations for Health Care Consumers

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Facts About Cellular Therapies

Sangamo has significant experience in process development and manufacturing of modified cell therapy products gained through its T-cell and hematopoietic stem cell (HSC) programs in HIV, which were the first genome editing products to enter human clinical trials. In collaboration with Bioverativ we are also developing modified HSC treatments for beta-thalassemia and sickle cell disease. Cells are removed from the body and undergo ZFN-mediated genome editing. In these autologous therapies, the modified cells are grown and tested before being infused back into the patient.

Modified T-cells have demonstrated spectacular success in treating some cancers. With the exception of two cases these have been autologous therapies. A more useful product would be an off-the-shelf or allogeneic product that could be administered to any patient on diagnosis rather than after precious weeks of manufacturing their own cells. Using our ZFN-mediated genome editing technology to knock out genes that identify these cells as foreign to a patient, we are working to make this possibility a reality.

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Cell Therapy :: Sangamo Therapeutics, Inc. (SGMO)

LONDON (Reuters) - French cell therapy specialist Cellectis, which is developing a gene-modified cancer treatment similar to Novartiss recently approved Kymriah, has been forced to suspend testing following a patient death.

Cellectis said on Tuesday it was working closely with the U.S. Food and Drug Administration in order to resume trials with a lower dose of the medicine UCART123.

Shares in the company fell 26 percent in morning trade following the U.S. regulators decision to place a so-called clinical hold on two early-stage trials of the medicine in blood cancers.

Novartis made history last week when it won approval for its $475,000 drug Kymriah, the first in a new class of treatments called CAR-T immunotherapies that use modified disease-fighting T cells to attack cancer.

While Novartis and rivals such as Juno and Kite use cells from the patients own body, Cellectiss gene edited cell therapy product offers an off-the-shelf, or allogeneic, option by deriving cells from healthy donors.

It is designed to help patients with acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN).

However, the first patient treated in the BPDCN study, a 78-year-old man, died after experiencing cytokine release syndrome (CRS), a dangerous release of cell-signaling proteins.

The first patient treated in the AML trial, a 58-year-old woman, also experienced CRS and other symptoms but recovered.

Jefferies analysts said there was a chance that the adverse CRS events could be mitigated by lowering the dose and treating symptoms more aggressively, but more information was needed to assess prospects for UCART123.

The side effects could be caused in part by the fact that UCART123 cells come from a healthy donor, rather than the patients own body, they added.

Cellectis, which was founded in 1999, is also working on another off-the-shelf cell therapy called UCART19, which is being developed with Servier and Pfizer. That product is now being tested in trials for acute lymphoblastic leukemia.

UCART19 has already rescued two babies treated at Londons Great Ormond Street Hospital from previously incurable cancer.

Reporting by Ben Hirschler; editing by Jason Neely and Louise Heavens

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France's Cellectis told to pause cell therapy tests after death - Reuters

LONDON (Reuters) - French cell therapy specialist Cellectis, which is developing a gene-modified cancer treatment similar to Novartiss recently approved Kymriah, has been forced to suspend testing following a patient death.

Cellectis said on Tuesday it was working closely with the U.S. Food and Drug Administration in order to resume trials with a lower dose of the medicine UCART123.

Shares in the company fell 26 percent in morning trade following the U.S. regulators decision to place a so-called clinical hold on two early-stage trials of the medicine in blood cancers.

Novartis made history last week when it won approval for its $475,000 drug Kymriah, the first in a new class of treatments called CAR-T immunotherapies that use modified disease-fighting T cells to attack cancer.

While Novartis and rivals such as Juno and Kite use cells from the patients own body, Cellectiss gene edited cell therapy product offers an off-the-shelf, or allogeneic, option by deriving cells from healthy donors.

It is designed to help patients with acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN).

However, the first patient treated in the BPDCN study, a 78-year-old man, died after experiencing cytokine release syndrome (CRS), a dangerous release of cell-signaling proteins.

The first patient treated in the AML trial, a 58-year-old woman, also experienced CRS and other symptoms but recovered.

Jefferies analysts said there was a chance that the adverse CRS events could be mitigated by lowering the dose and treating symptoms more aggressively, but more information was needed to assess prospects for UCART123.

The side effects could be caused in part by the fact that UCART123 cells come from a healthy donor, rather than the patients own body, they added.

Cellectis, which was founded in 1999, is also working on another off-the-shelf cell therapy called UCART19, which is being developed with Servier and Pfizer. That product is now being tested in trials for acute lymphoblastic leukemia.

UCART19 has already rescued two babies treated at Londons Great Ormond Street Hospital from previously incurable cancer.

Reporting by Ben Hirschler; editing by Jason Neely and Louise Heavens

Link:
Cellectis shares slump as death puts cell therapy tests on hold - Reuters

The US FDA has ordered Cellectis SA to halt studies of its cell therapy UCART123 after the death of a patient.

Cellectis announced the clinical hold yesterday, explaining it applied to both Phase I studies known as ABC123 and AML123 - in which the therapy is being examined.

The deceased man - a 78 year old in the ABC study who was suffering with relapsed blastic plasmacytoid dendritic cell neoplasm (BPDCN) died nine days after receiving the first dose of UCART123.

According to Cellectis, after a preconditioning regimen involving fludarabine and cyclophosphamide, the patient was treated with UCART123 on August 16.

Five days later he experienced a grade 2 Cytokine Release Syndrome (CRS) and a grade 3 lung infection which improved after treatment with tocilizumab and antibiotics.

However, at day eight the patient experienced a grade 5 CRS event and grade 4 Capillary Leak Syndrome that did not respond to corticosteroids and tociluzumab. He died the following day.

Cellectis also revealed the first patient treated in the AML study, a 58-year old woman suffering acute myeloid leukemia who received the same preconditioning regimen and the same dose of UCART123, had recoveered after experiencing similar complications.

According to the firm She experienced an initial grade 2 CRS at Day 8, worsening to a grade 3 at Day 9 and resolving at Day 11 with treatment management in intensive care unit. She also experienced a grade 4 Capillary Leak Syndrome at Day 9, resolved at Day 12.

Cellectis said it is working closely with the investigators and the FDA in order to resume the trials with an amended protocol including a lowered dosing of UCART123.

Background

UCART123 consists of T-cells modified to target the CD123 antigen on the surface of cancerous cells.

The therapy which is made on Cellectis behalf by the LFB Group subsidiary CELLforCURE- is produced using Talen gene editing to insert genes that encode a chimeric antigen receptor (CAR) that targets the CD123 antigen.

Unlike autologous cell therapies made from the specific patients own cells, UCART123 is composed of lymphocytes harvested from an unrelated, so called universal donor.

According to Cellectis, Talen gene editing prevents the T-cells from interacting with non-target proteins, thereby reducing side-effects

The US Food and Drug Administration (FDA) cleared Cellectis to start trialling UCART123 in February.

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US FDA tells Cellectis to halt cell therapy trials after patient death - In-PharmaTechnologist.com

Zika, notorious for ravaging the brains of babies, could be useful in treating a particularly deadly brain cancer.

The virus kills glioblastoma stem cells, say researchers at UC San Diego and Washington University in St. Louis. They tested in human cell cultures and a mouse model of the disease

Moreover, Zika largely spared mature brain cells, the researchers say in a study published Tuesday in the Journal of Experimental Medicine.

People with glioblastoma rarely survive more than two years, although survival rates vary according to age and how aggressive the tumor is.

Study authors suggest a tamed version of the virus could be used along with other treatment to improve survival rates.

U.S. Senator John McCain was recently diagnosed with glioblastoma. The disease killed U.S. Senator Ted Kennedy, singer-actress Ethel Merman and retired baseball player Gary Carter.

Glioblastomas are treated with surgery, followed by radiation and chemotherapy. However, it is impossible to remove all the cancer without also removing healthy tissue and risking brain damage. So the cancer nearly always comes back.

Cancer stem cells cause the recurring tumors. These cells bear strong genetic resemblances to normal stem cells, and can proliferate greatly. Just one cell can regrow an entire tumor.

Glioblastoma stem cells also resist chemotherapy and radiation. But because they are stem cells, they are vulnerable to Zika. The virus causes an abnormally small head, or microcephaly, by destroying immature neural cells.

The study authors say a modified Zika virus could be applied after surgery, penetrating to the remaining cancer cells and killing them. One author, Jeremy Rich, M.D., is a renowned brain cancer specialist who recently joined UC San Diego from Cleveland Clinic. The first author, Zhe Zhu, also researches at UCSD.

Brain cancer specialists not involved with the study said by email it is scientifically sound, but there is a long way to go before it could be used in patients.

The science in this study is good considering the limitations of test tube and mice models, said Keith Black, M.D., chair of neurosurgery at Cedars-Sinai Medical Center in Los Angeles. What we don't know is how these results will translate to humans, given how different the complex human tumors are compared to simplistic mice models.

Before a Zika-based therapy can be tested in people, toxicity studies need to be completed in animals, along with regulatory approvals from the U.S. Food and Drug Administration and the institutes where the trial is to be conducted, Black said.

The approach has precedent in viral therapy by San Diegos Tocagen to treat glioblastoma, said Faith Barnett, M.D., a neurosurgeon with Scripps Green Hospital in La Jolla. Tocagens therapy is already being tested on glioblastoma patients. It uses poliovirus and retroviruses, a class of virus that includes HIV.

Whether Zika virus is a better vector needs to be determined, Barnett said. Clearly, we need creative approaches to improve current cancer therapies.

Unlike Zika, Tocagens viruses dont directly attack the brain cancer cells. Instead, they deliver a gene to the cancer that primes it for destruction when exposed to a drug precursor or prodrug.

The prodrug is converted into a toxic drug inside the cancer cells through an enzyme the gene codes for. Normal cells dont get the gene, and so are unaffected by the prodrug.

Go online to http://tocagen.com/patients for more information on Tocagens clinical trials.

For further reading

McCain completes round of radiation, chemo for brain cancer

UC San Diego hires renowned brain cancer expert Jeremy Rich

Blocking a tumor suppressor gene actually slows down one kind of glioblastoma

Survival time increases for those with deadly brain cancer: Study

Cancer genes hide outside chromosomes

Mom delays cancer care to protect baby she says saved her

Gary Carter to treat brain tumor with chemotherapy

Glioblastoma Anti-Angiogenesis Resistance Mechanism Found by Salk Researchers

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Zika kills brain cancer cells, may find use as therapy - The San Diego Union-Tribune