Melanoma-associated antigen peptide-MHC complex (MAA-pMHC)

Melanoma-associated antigen (MAA) peptide-MHC complexes are the primary targets for T-cell-mediated immunotherapy in melanoma. These complexes consist of short peptides derived from intracellular melanoma proteins—such as gp100, MART-1, MAGE-A3, and NY-ESO-1—bound to Major Histocompatibility Complex (MHC) molecules on the cell surface (Vigneron, 2015). On dendritic cells, these complexes serve to prime and activate naive T cells, a process often exploited in dendritic cell vaccines to generate a systemic anti-tumor immune response (Banchereau & Palucka, 2005). In the tumor microenvironment, the same complexes on melanoma cells are recognized by cytotoxic T cells, leading to tumor cell lysis. Therapeutic strategies targeting these complexes include peptide vaccines, adoptive T-cell transfer (TCR-T), and bispecific T-cell engagers like tebentafusp, which specifically targets the gp100 peptide presented by HLA-A*02:01 (Nathan et al., 2021). The clinical utility of these targets is often restricted by the patient's HLA type, as the peptide must fit into a specific MHC allele's binding groove to be presented effectively (FDA KIMMTRAK Label).

Other names

Melanoma-associated antigensMAATumor-associated antigen peptide-MHC complexpMHCMelanoma antigen-derived peptidesCancer-testis antigen peptide-MHC complex

Drugs targeting these complexes act as T-cell redirectors or vaccines. Vaccines deliver antigens to dendritic cells to promote the formation of these complexes for T-cell priming. Soluble T-cell receptors (TCRs) or TCR-engineered T cells (TCR-T) directly bind to the peptide-MHC complex on the surface of tumor cells to initiate targeted cell lysis.