Sangamo Therapeutics has been granted authorisation from the UK’s Medicines Healthcare Products Regulatory Agency (MHRA) to conduct the first-in-human clinical trial of a novel type of cell therapy - Chimeric Antigen Receptor Regulatory T Cell (CAR-Treg).
The drug, TX200, is being evaluated for the prevention of immune-mediated rejection following HLA-A2 mismatched kidney transplantation for end-stage renal disease (ESRD).
The genomic medicine company says it expects to open the first clinical sites for the STEADFAST study in 2020, which makes it the “first company to test a CAR-Treg candidate in humans” according to Adrian Woolfson, head of research and development at Sangamo. He went on to say the regulatory announcement marks an “important milestone for Sangamo and an exciting new frontier of cellular therapy.”
“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. Beyond transplantation, we plan to explore the potential of CAR-Tregs in a range of autoimmune and inflammatory diseases.”
The therapy in question is an “autologous HLA-A2-targeted CAR-Treg cell therapy”. During kidney transplantation, the patient’s regulatory T cells (Tregs), a type of white blood cell which plays a key role in regulating the immune response and inflammation, are collected and genetically engineered with a Chimeric Antigen Receptor (CAR) designed to bind to HLA-A2.
As a result, sometimes donor or recipient mismatch in HLA molecules is a primary contributor to organ transplant incompatibility and may ultimately lead to immune-mediated rejection of the transplanted organ.
This is where TX200 comes in; The new technology is designed to accumulate and localise within the new kidney where the HLA‑A2 protein is present, thereby utilising the ability of Tregs to suppress immune responses against the transplanted kidney.
Kidney transplantation is the treatment of choice for patients with ESRD who must otherwise remain on long-term dialysis. To prevent graft rejection, transplanted patients are treated with lifelong immune suppressive therapy, which impacts the body’s immune system broadly and is associated with multiple side effects.