Sangamo to Launch First-in-human Clinical Trial Testing TX200 Cell Therapy in End-stage Renal Disease

Sangamo to Launch First-in-human Clinical Trial Testing TX200 Cell Therapy in End-stage Renal Disease

The United Kingdom’s Medicines Healthcare Products Regulatory Agency (MHRA) has authorized the first-in-human clinical trial testing Sangamo TherapeuticsTX200, a cell-based CAR-Treg therapy, in preventing rejection of transplanted kidneys in patients with end-stage renal disease (ESRD).

Alport syndrome patients are at high risk of developing end-stage kidney disease, the last stage of chronic kidney disease, at which time the kidneys are damaged so badly they no longer function. ESRD usually is managed with dialysis, but some patients eventually may require a kidney transplant.

After a transplant, there is a risk that the patient’s immune system will recognize the transplanted organ as foreign, resulting in rejection. One of the main reasons why organ transplant incompatibility occurs is due to a mismatch in human leukocyte antigen (HLA) proteins between the organ donor and recipient. This mismatch may be recognized by the immune system, resulting in the new kidney being attacked.

To prevent organ rejection, patients take immunosuppressant medications,  which act to dampen the immune response and decreasing chances of the new organ being targeted. However, these therapies have several side effects.

TX200 is a CAR (chimeric antigen receptor) T-cell therapy, consisting of a subset of regulatory T cells collected from the patient and engineered to target HLA-A2, a type of HLA protein. (Regulatory T cells are a type of white blood cell involved in managing the immune response and inflammation.)

By binding to HLA-A2, the TX200 therapy will accumulate in the new kidney where the HLA-A2 protein is present, suppressing immune responses against the transplanted kidney. It is hoped that the therapy will induce immune tolerance and potentially lead to the reduction and eventual elimination of immunosuppressant medications.

The potential of TX200 in preventing immune-mediated kidney transplant rejection will be assessed in a multi-center, open-label, Phase 1/2 clinical study called STEADFAST.

The trial, which will test single ascending doses of TX200, will be carried out in the United Kingdom, France, Netherlands, Germany and Belgium. It is expected the first clinical sites will be opened in 2020.

“Being the first company to test a CAR-Treg candidate in humans is an important milestone for Sangamo and this exciting new frontier of cellular therapy,” Adrian Woolfson, head of research and development at Sangamo, said in a press release. “We believe that the TX200 program will be invaluable in expanding our understanding of the safety and mechanism of action of CAR-Treg cells and their relevance in the clinic.”

He also said “This innovative and personalized cellular therapy approach for HLA-A2 mismatched kidney transplantation is designed to help regulate the body’s immune system specifically and locally to promote acceptance of an immunologically mismatched donor organ. Beyond transplantation, we plan to explore the potential of CAR-Tregs in a range of autoimmune and inflammatory diseases.”

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.