autologous MART-1-specific TCR-transduced T cells

Autologous MART-1-specific TCR-transduced T cells is a target-specific adoptive cell therapy platform (TCR-engineered T cell therapy) developed by multiple institutions, most notably the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI-AVL) and the National Cancer Institute (NCI), for the treatment of metastatic melanoma. The therapy involves isolating a patient's own peripheral blood T cells via apheresis, activating them, and transducing them with a retroviral or lentiviral vector encoding a MART-1-specific T-cell receptor (TCR). In a prominent clinical trial by NKI-AVL (NCT02654821), T cells were transduced with a retroviral vector encoding a modified MART-1(26-35)-specific TCR (1D3HMCys) and expanded ex vivo in the presence of IL-7 and IL-15. Patients received non-myeloablative lymphodepleting chemotherapy followed by a single intravenous infusion of the engineered T cells and low-dose interleukin-2. However, clinical development of the NKI-AVL candidate was limited by severe dose-dependent on-target, off-tumor toxicities (affecting the skin, eyes, and ears) and cytokine release syndrome, resulting in a maximum tolerated dose of 1.0 x 10^8 transduced cells.

Other names

MART-1 TCR-transduced autologous T-cell therapyMART1 TCR-transduced autologous T-cell therapyMART 1 TCR-transduced autologous T-cell therapyMART-1 TCR gene-modified peripheral blood T cellsMART1 TCR gene-modified peripheral blood T cellsMART 1 TCR gene-modified peripheral blood T cellsautologous T cells genetically transduced with a MART-1-specific T-cell receptor