Melan-A (MLANA) peptide ELAGIGILTV-specific T-cell receptor restricted by HLA-A*02:01 (MLANA-specific TCR)

The CD8+ T-cell receptor (TCR) recognizing the MLANA (Melan-A/MART-1) peptide ELAGIGILTV presented by HLA-A*02:01 is a specialized immune receptor used in cancer immunotherapy to target melanoma. MLANA is a melanocyte differentiation antigen that is highly expressed in the majority of melanoma tumors, making it an attractive target for T-cell-based therapies (UniProt: Q16655). The ELAGIGILTV peptide is a modified heteroclitic analog of the natural MART-1 26-35 epitope, designed with an amino acid substitution at the first position to enhance its binding affinity to the HLA-A*02:01 molecule and improve T-cell recognition (PubMed: 9491715). Plasmacytoid dendritic cells (pDCs) are particularly efficient at presenting this antigen to CD8+ T cells, facilitating the priming and expansion of high-avidity T-cell populations (PubMed: 21624935). In clinical applications, patient T cells are engineered to express this specific TCR to induce a potent cytotoxic response against melanoma cells. However, because MLANA is also expressed in healthy melanocytes, therapeutic use of these TCRs can lead to on-target, off-tumor toxicities such as vitiligo, uveitis, and hearing loss (PubMed: 19633199).

Other names

MART-1-specific T-cell receptorHLA-A*02:01/ELAGIGILTV-specific TCRMelan-A-specific TCRMART-1 TCR

Adoptive cell transfer of TCR-engineered T cells that recognize and lyse HLA-A*02:01-positive cells expressing the MLANA antigen.