Melanoma antigen recognized by T-cells 1 (26-35) (MART-1 (26-35))

Melanoma antigen recognized by T-cells 1 (MART-1), also known as Melan-A, is a lineage-specific protein essential for the expression and stability of Pmel17/gp100 in melanosomes (UniProt: Q16655). The 26-35 peptide fragment (sequence: EAAGIGILTV) is a highly immunodominant epitope that is frequently presented by the Human Leukocyte Antigen (HLA)-A*02:01 allele in patients with melanoma (PubMed: 8021017). Due to its high expression in over 80% of melanomas and its restricted expression in normal melanocytes, this peptide has become a primary target for cancer immunotherapies, including peptide-based vaccines and T-cell receptor (TCR) engineered cell therapies (PubMed: 9430502). In clinical applications, a modified version of the peptide known as A27L (sequence: ELAGIGILTV) is often utilized because it possesses a higher binding affinity for the HLA molecule, thereby inducing a more robust T-cell response (PubMed: 10444431). While therapeutic targeting of the MART-1:26-35 peptide has shown success in inducing tumor regression, it is frequently associated with on-target, off-tumor toxicities affecting normal melanocytes in the skin, eyes, and ears, leading to conditions such as vitiligo and uveitis (PubMed: 19139129). This target remains a cornerstone in the study of antigen-specific T-cell responses and the development of adoptive cell transfer technologies for solid tumors.

Other names

Melan-A (26-35)MART-1:26-35 peptideMART1 peptideEAAGIGILTVELAGIGILTV (A27L modified variant)Antigen LB39-AAAntigen SK29-AA

The peptide acts as an epitope presented by HLA-A*02:01 molecules on the surface of tumor cells, where it is recognized by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, leading to targeted cell lysis.