tacrolimus-resistant autologous Epstein-Barr virus-specific cytotoxic T lymphocytes

This cell therapy consists of autologous cytotoxic T lymphocytes (CTLs) that have been selectively expanded and genetically modified to recognize Epstein-Barr virus (EBV) antigens while remaining resistant to the immunosuppressive effects of tacrolimus (FK506). The CTLs are typically trained to target EBV latent membrane proteins (LMP1, LMP2) and the EBV nuclear antigen (EBNA1). To enable these cells to function in the immunosuppressive environment of a solid organ transplant recipient, they are modified—often via a retroviral vector—to express a mutated form of calcineurin that does not bind the tacrolimus-FKBP12 complex, or alternatively, by knocking down FKBP12 using RNA interference. This engineering preserves T-cell receptor (TCR) signaling and cytotoxic effector functions, allowing the cells to proliferate and eliminate EBV-infected cells or EBV-positive lymphoma cells even while the patient is maintained on therapeutic doses of tacrolimus to prevent graft rejection. The therapy is primarily developed by researchers at Baylor College of Medicine for the treatment of EBV-associated post-transplant lymphoproliferative disorder (PTLD).

Other names

tacrolimus-resistant EBV-CTLstacrolimus-resistant autologous EBV-specific CTLscalcineurin-resistant EBV-CTLs