MART-1-specific T cell receptor (MART-1 TCR)

The MART-1-specific T cell receptor (TCR) is a specialized protein complex responsible for recognizing the Melanoma Antigen Recognized by T cells 1 (MART-1), also known as Melan-A. This recognition occurs when the MART-1 peptide, typically the immunodominant decamer AAGIGILTV, is presented by the Human Leukocyte Antigen (HLA)-A*02:01 molecule on the surface of tumor cells (PMID: 16946075). In the context of cancer immunotherapy, this TCR is a primary target for TCR-engineered T cell therapy (TCR-T), where a patient's own T cells are genetically modified to express a high-affinity MART-1-specific TCR to enhance anti-tumor immunity (PMID: 19147751). While MART-1 is highly expressed in most melanomas, it is also present in normal melanocytes found in the skin, retina, and inner ear. Consequently, therapeutic targeting of this TCR can lead to on-target, off-tumor toxicities, such as vitiligo, uveitis, and hearing loss, which represent significant clinical challenges (PMID: 21417915). Despite these risks, MART-1 remains a benchmark antigen for developing and testing adoptive cell transfer technologies and understanding T cell-mediated tumor regression (PMID: 23303620).

Other names

T cell receptor on MART-1-specific CD8+ T cellsMelan-A-specific T cell receptorMART-1-reactive TCRTCR-MART-1HLA-A2/MART-1 TCR

Adoptive transfer of T cells engineered to express a high-affinity TCR that recognizes the MART-1 peptide (AAGIGILTV) presented by HLA-A*02:01, leading to targeted lysis of melanoma cells (PMID: 16946075, PMID: 19147751).