Melan-A-specific T-cell receptor (Melan-A TCR)

The Melan-A-specific T-cell receptor (TCR) is a specialized heterodimeric protein complex expressed on the surface of CD8+ cytotoxic T-lymphocytes that specifically recognizes the Melan-A (also known as MART-1) peptide presented by the Human Leukocyte Antigen (HLA)-A*0201 molecule (UniProt, 2024). Melan-A is a melanocyte differentiation antigen that is highly expressed in the majority of malignant melanomas, making it a significant target for cancer immunotherapy (Rosenberg et al., 2006, Science). Upon binding to the Melan-A/HLA-A*0201 complex on tumor cells, the TCR triggers a signaling cascade that leads to T-cell activation, cytokine release, and the targeted destruction of the melanoma cell (Johnson et al., 2009, Blood). Therapeutic strategies targeting this receptor include adoptive cell transfer using TCR-engineered T-cells (TCR-T) and soluble bispecific molecules like ImmTACs (ClinicalTrials.gov). However, because Melan-A is also expressed in healthy melanocytes within the skin, eye, and inner ear, therapeutic targeting can lead to on-target, off-tumor toxicities such as vitiligo, uveitis, and hearing loss. Patient selection for these therapies requires screening for the HLA-A*0201 allele and confirmed tumor expression of the Melan-A antigen.

Other names

MART-1-specific T-cell receptorMelan-A/HLA-A*0201-specific TCRMelanoma antigen recognized by T-cells 1-specific T-cell receptorMART-1 TCR

Adoptive T-cell transfer (TCR-T) and bispecific T-cell engagement to induce targeted lysis of Melan-A-expressing tumor cells.