Melanoma antigen recognized by T cells 1 (MART-1) peptide presented by Human Leukocyte Antigen A*02:01 (HLA-A*02:01) (MART-1/HLA-A2)

The MART-1/Melan-A peptide presented by HLA-A2 is a well-characterized peptide-major histocompatibility complex (pMHC) target primarily utilized in the immunotherapy of metastatic melanoma (Kawakami et al., 1994, PubMed: 7506951). MART-1 (Melanoma Antigen Recognized by T cells 1), encoded by the MLANA gene, is a melanocyte differentiation antigen that is highly expressed in both normal melanocytes and the majority of melanoma tumors (UniProt: Q16655). The specific immunodominant peptide, often MART-1(26-35), is processed and displayed on the cell surface by the HLA-A*02:01 allele, where it can be recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes. This complex has been the focus of numerous clinical strategies, including the development of TCR-engineered T-cell (TCR-T) therapies and peptide-based vaccines designed to elicit a robust anti-tumor immune response (Johnson et al., 2009, PubMed: 19171878). However, because MART-1 is also present in healthy melanocytes in the skin, eye, and inner ear, therapeutic targeting of this complex is associated with specific on-target, off-tumor toxicities such as vitiligo, uveitis, and hearing loss (Johnson et al., 2009, PubMed: 19171878). Despite these safety considerations, the MART-1/HLA-A2 complex remains a benchmark target for evaluating the efficacy and safety of novel T-cell-based modalities in the field of adoptive cell transfer.

Other names

Melan-A peptide/HLA-A2 complexMART-1(26-35)/HLA-A2MLANA/HLA-A2MART-1/HLA-A*02:01Melanoma antigen recognized by T cells 1 peptide/HLA-A2 complex

Recognition of the MART-1 peptide/HLA-A2 complex by engineered or endogenous T-cell receptors (TCRs), which triggers the activation of cytotoxic T lymphocytes (CTLs) and the subsequent release of perforins, granzymes, and cytokines to induce apoptosis in melanoma cells (PubMed: 19171878).