The therapy was originally developed in collaboration with Megan Levings, PhD, a professor at the University of British Columbia, in Canada, whose research has focused on a new subset of CD4+ T cells, termed T regulatory or Treg cells. Treg cells control immune homeostasis.
aHUS is a genetic disease that leads to the accumulation of blood clots inside the kidneys. These may block blood flow and cause hemolytic anemia and thrombocytopenia. In more severe cases, such accumulations leads to end-stage kidney disease, in which the only option is dialysis or a kidney transplant.
How does TX200 work?
TX200 consists of patients’ own regulatory T cells (Tregs), a type of white blood cell that plays an important role in suppressing the immune response and inflammation, which have been genetically engineered with a chimeric antigen receptor (CAR) designed to bind to HLA-A2, a protein that belongs to the human leukocyte antigen (HLA) system.
When a patient receives an organ transplant, the organ’s acceptance in the body depends on the compatibility between the donor’s and the recipient’s HLA molecules. If the donor’s and the recipient’s HLA molecules do not match, the transplanted organ is identified as foreign by the recipient’s immune system. In such cases, the transplanted organ is attacked, leading to its rejection.
A chimeric antigen receptor-regulatory T cell (CAR-Treg) therapy, TX-200 is designed to allow the accumulation of engineered CAR-Tregs within the transplanted kidney. Since the CAR-Tregs bind specifically to the HLA-A2 protein, they can potentially suppress the immune response and prevent an immune attack on the transplanted kidney. Thus, TX200 aims to increase recipients’ immune tolerances and potentially help their bodies accept the new kidneys. It also can potentially eliminate, or at least reduce, the need for immunosuppressive treatments that usually accompany kidney transplants.
TX200 in clinical trials
Sangamo is now planning to initiate an open-label, multicenter, single-dose ascending, dose-ranging Phase 1/2 study. That trial will evaluate the effect of TX200 in preventing the development of an immune response following HLA-A2 mismatched kidney transplants in patients with end-stage kidney disease.
Called the STEADFAST study, it will take place at five sites in Europe, in the U.K., France, the Netherlands, Germany, and Belgium.
Last updated: Feb. 3, 2020
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