Melanoma-associated antigen presented on Major Histocompatibility Complex (MAA-MHC) (MAA-MHC)

Melanoma-associated antigen (MAA) presented on the Major Histocompatibility Complex (MHC) refers to a class of intracellular proteins processed into peptides and displayed on the cell surface for T-cell recognition. These targets include cancer-testis antigens (CTAs) like MAGE-A4 and NY-ESO-1, which exhibit high tumor specificity, and differentiation antigens like gp100 and MART-1, which are shared with normal melanocytes (Nature Reviews Cancer, 2021). Because these antigens are presented by MHC molecules, they allow the immune system to target internal cellular proteins that are otherwise inaccessible to traditional antibody-based therapies (Journal for ImmunoTherapy of Cancer, 2020). Therapeutic strategies such as T-cell receptor (TCR) engineered T-cells and bispecific T-cell engagers (ImmTACs) are designed to bind these specific peptide-MHC complexes with high affinity. For instance, Tebentafusp is an approved bispecific protein targeting the gp100 peptide presented by HLA-A*02:01 in uveal melanoma (FDA, 2022). Afamitresgene autoleucel is another recently approved TCR-T therapy targeting the MAGE-A4 peptide in synovial sarcoma, a target also prevalent in melanoma (FDA, 2024). While highly promising, these therapies require patients to possess specific HLA alleles, most commonly HLA-A*02:01, which limits the eligible patient population. Furthermore, they carry risks of cytokine release syndrome or off-target toxicity if the target peptide sequence mimics proteins in healthy tissues (Frontiers in Immunology, 2021).

Other names

Cancer-testis antigenTumor-associated antigenpMHC complexMelanoma antigen familyMAGENY-ESO-1PRAMEgp100

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