Melanoma antigen recognized by T cells 1 (MART-1) peptide-HLA complex (MART-1/Melan-A-HLA)

MART-1 (Melanoma Antigen Recognized by T cells 1), also known as Melan-A, is a lineage-specific differentiation antigen primarily expressed in melanocytes and melanoma cells (UniProt: Q16655). The therapeutic target is the specific peptide fragment (epitope), most commonly the decamer AAGIGILTV or nonamer ELAGIGILTV, presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, typically HLA-A*02:01 (PubMed: 8175760). This peptide-MHC complex is recognized by the T-cell receptor (TCR) of cytotoxic T lymphocytes, making it a prominent target for cancer immunotherapies (PubMed: 19147750). In melanoma, MART-1 is highly and frequently expressed, providing a window for targeted destruction of tumor cells (UniProt: Q16655). However, because MART-1 is also expressed in healthy melanocytes in the skin, eye, and inner ear, therapies targeting this complex can lead to on-target off-tumor toxicities such as vitiligo, uveitis, and hearing loss (PubMed: 19147750). Current drug development efforts include TCR-engineered T-cell therapies (TCR-T), peptide-based vaccines, and bispecific T-cell engagers designed to redirect the immune system against MART-1-positive cells (ClinicalTrials.gov: NCT00070343).

Other names

MART-1Melan-AMLANAMelanoma antigen recognized by T-cells 1MART1

T-cell receptor (TCR) mediated recognition of the peptide-HLA complex, triggering cytotoxic T-lymphocyte activation and targeted lysis of cells expressing the antigen.