Melanoma-associated antigen (MAA) (MAA)

Melanoma-associated antigens (MAAs) are a group of proteins expressed by melanoma cells that can be recognized by the immune system when presented as peptides on Major Histocompatibility Complex (MHC) molecules. This presentation is primarily facilitated by dendritic cells, which prime T-cell receptors (TCRs) to identify and destroy malignant cells (Kawakami et al., 1994, PubMed: 8175760). MAAs include differentiation antigens like MART-1 and gp100, which are also found in normal melanocytes, and cancer-testis antigens like MAGE-A3 and NY-ESO-1, which are typically tumor-specific (Boon et al., 1994, PubMed: 8124711). These antigens serve as the foundation for various immunotherapies, including dendritic cell vaccines, TCR-engineered T-cell (TCR-T) therapies, and immune-mobilizing monoclonal T-cell receptors against cancer (ImmTACs) like tebentafusp (Nathan et al., 2022, NEJM). While these therapies leverage the specificity of the TCR-peptide-MHC interaction, they face challenges such as HLA restriction and "on-target, off-tumor" toxicities, most notably vitiligo and uveitis, resulting from the destruction of healthy melanocytes (Yeh et al., 2009, PubMed: 19440291).

Other names

Tumor-associated melanoma antigenMelanoma antigenCancer-testis antigenDifferentiation antigenMAATAA

Antigen presentation to T-cell receptors via MHC molecules