Melanoma tumor-associated antigen-major histocompatibility complex (Melanoma TAA-MHC) (Melanoma TAA-MHC)

Melanoma tumor-associated antigens (TAAs) presented by the Major Histocompatibility Complex (MHC) are intracellular proteins processed into peptides and displayed on the cell surface for recognition by T-cell receptors (TCRs) (National Cancer Institute). These antigens are broadly classified into differentiation antigens, such as MART-1 and gp100, and cancer-testis antigens like NY-ESO-1 and MAGE-A4 (Vigneron, BioMed Research International, 2015). The interaction between a specific TCR and the peptide-MHC (pMHC) complex is the primary trigger for cytotoxic T-lymphocyte activation and subsequent tumor cell lysis (Abbas, Cellular and Molecular Immunology). In therapeutic contexts, this interaction is exploited through TCR-engineered T-cell (TCR-T) therapies and bispecific TCR molecules, such as tebentafusp, which targets gp100 (Nathan et al., NEJM, 2021). These therapies typically require specific HLA-type matching, most commonly HLA-A*02:01, and confirmed expression of the target antigen on the tumor (D'Angelo et al., Cancer Discovery, 2018). Safety concerns include on-target off-tumor toxicity, where T cells attack healthy tissues expressing the same antigens, and systemic inflammatory responses like cytokine release syndrome (Merchant et al., The Lancet, 2024).

Other names

Melanoma-associated antigen (MAA)Melanoma differentiation antigenCancer-testis antigen (CTA)Melanoma neoantigenPeptide-MHC complex (pMHC)

T-cell receptor (TCR) mediated recognition of peptide-MHC complexes leading to cytotoxic T-lymphocyte activation and tumor cell lysis.