Melanoma-associated antigen peptide-HLA-A*02:01 complex (MAA-HLA-A2)

The Melanoma-associated antigen peptide-HLA-A*02:01 complex is a specialized molecular target consisting of an intracellularly derived peptide fragment bound to the Human Leukocyte Antigen (HLA) class I molecule A*02:01. These peptides originate from proteins overexpressed in melanoma cells, such as MAGE-A3, MART-1, and gp100, which are processed by the proteasome and transported to the cell surface (Schadendorf et al., 2018). The resulting peptide-MHC (pMHC) complex acts as a critical recognition site for the immune system, specifically targeted by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (Hassan et al., 2022). In healthy tissues, these specific melanoma-associated antigens are typically not expressed or are restricted to immune-privileged sites, making the pMHC complex a highly specific target for advanced immunotherapies (Thomas et al., 2023). Therapeutic strategies targeting this complex include TCR-engineered T-cell therapies (TCR-T) and immune-mobilizing monoclonal TCRs against cancer (ImmTACs). For example, tebentafusp is a bispecific molecule that redirects T-cells to attack gp100-expressing melanoma cells by binding specifically to the gp100:HLA-A*02:01 complex (Nathan et al., 2021). Similarly, afamitresgene autoleucel utilizes engineered TCRs to target MAGE-A4 peptides presented on HLA-A2 (D'Angelo et al., 2018). The clinical efficacy of these treatments is strictly dependent on the patient possessing the HLA-A*02:01 allele and the tumor expressing the relevant parent antigen, necessitating precise patient selection through companion diagnostics.

Other names

pMHC complexPeptide-MHC complexMAGE-HLA-A2 complexMART-1-HLA-A2 complexgp100-HLA-A2 complexNY-ESO-1-HLA-A2 complexHLA-A*02:01-restricted melanoma antigen

T-cell receptor (TCR) redirection, Bispecific T-cell engagement, Adoptive cell therapy (TCR-T)