Melanoma antigen recognized by T cells 1 specific T cell receptor (MART-1 TCR)

The T cell receptor (TCR) recognizing MelanA-derived peptide (also known as MART-1) is a specialized immune receptor utilized in adoptive cell therapies for metastatic melanoma. MelanA is a melanocyte differentiation antigen highly expressed in melanoma cells but restricted in normal tissues to melanocytes in the skin, eye, and inner ear (Kawakami et al., 1994, PNAS). The TCR is engineered or selected to recognize the MelanA peptide, typically the ELAGIGILTV sequence, presented by the HLA-A*02:01 major histocompatibility complex (MHC) (Johnson et al., 2009, Blood). In some therapeutic contexts, autologous dendritic cells are used to present these peptides to T cells to stimulate a robust, patient-specific immune response. Upon binding to the peptide-MHC complex on tumor surfaces, the TCR initiates T-cell activation and the secretion of cytotoxic cytokines and granules to eliminate the cancer cells. Clinical trials have demonstrated that MART-1 TCR-engineered T cells can induce significant tumor regression in patients with advanced melanoma. However, the therapy is associated with on-target off-tumor toxicities, such as vitiligo and uveitis, due to the destruction of healthy melanocytes (Choudhary et al., 2012, Journal of Clinical Oncology).

Other names

MelanA-specific T cell receptorMART-1-specific TCRT cell receptor recognizing MelanA-derived peptideMART-1/Melan-A-specific T-cell receptor

Adoptive transfer of T cells expressing a TCR that recognizes the MelanA/MART-1 peptide-MHC complex, leading to targeted destruction of melanoma cells.