Melanoma-associated antigen peptide-Human Leukocyte Antigen complex (MAA-HLA)

Melanoma-associated antigens (MAAs) are a diverse group of proteins, including cancer-testis antigens (e.g., NY-ESO-1, MAGE family) and melanocyte differentiation antigens (e.g., gp100, MART-1), that are processed into short peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules [UniProt, National Cancer Institute]. These peptide-HLA (pMHC) complexes are the specific ligands recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T cells, triggering a targeted immune response against melanoma cells [PubMed: 24049118]. While HLA Class I molecules are the primary presenters to CD8+ T cells, HLA Class II molecules also present MAAs to CD4+ T cells, which are essential for maintaining a robust anti-tumor environment [PubMed: 30108117]. Therapeutic strategies targeting these complexes include TCR-engineered T-cell (TCR-T) therapies, such as Afamitresgene autoleucel, and bispecific T-cell engagers like Tebentafusp [FDA]. The clinical application of these drugs requires precise patient selection based on the presence of specific HLA alleles (e.g., HLA-A*02:01) and the expression of the target antigen within the tumor [FDA]. A major therapeutic challenge is "on-target, off-tumor" toxicity, which occurs if the targeted peptide is also presented by healthy tissues, potentially leading to severe adverse events [PubMed: 23918359].

Other names

Melanoma-associated antigenCancer-testis antigenDifferentiation antigenTumor-associated antigenpMHC complexPeptide-MHC complex

T-cell receptor (TCR) binding to peptide-MHC complex, T-cell mediated tumor cell lysis, and bispecific redirection of T cells.