Human leukocyte antigen A*02:01 (HLA-A*02:01) presenting Melanoma antigen recognized by T cells 1 (MART-1), Melanocyte lineage-specific antigen GP100 (gp100), and Tyrosinase peptides (HLA-A*02:01/Melanoma Antigen Complex)

The HLA-A*02:01 presenting MART-1, gp100, and tyrosinase peptides complex is a critical therapeutic target in the treatment of malignant melanoma. HLA-A*02:01 is a common Major Histocompatibility Complex (MHC) class I allele that presents intracellularly derived peptides to the cell surface for recognition by CD8+ cytotoxic T lymphocytes [UniProt P01892]. MART-1, gp100, and tyrosinase are melanocyte differentiation antigens that are frequently overexpressed in melanoma cells but are also present in healthy melanocytes [PubMed 21670456]. The presentation of these specific epitopes allows the immune system to identify and destroy cancerous cells through T-cell receptor (TCR) mediated recognition. Current therapeutic strategies include the use of bispecific TCR-fusion proteins like tebentafusp, which targets the gp100 peptide-HLA complex, and various TCR-engineered T-cell therapies and peptide vaccines [FDA, 2022; PubMed 21632993]. A significant challenge in targeting these complexes is the potential for autoimmune-like toxicities, such as vitiligo or uveitis, due to the expression of these antigens in normal skin and ocular tissues. Patient selection for these therapies requires confirmation of both the HLA-A*02:01 genotype and the expression of the relevant melanoma-associated antigens.

Other names

HLA-A2 restricted melanoma antigensMART-1/gp100/Tyrosinase peptide-MHC complexMelanocyte differentiation antigen-HLA complexesHLA-A*02:01/MART-1/gp100/TYR

Targeting of specific peptide-MHC complexes by engineered T-cell receptors (TCRs), bispecific T-cell engagers, or vaccines to induce cytotoxic T-lymphocyte (CTL) mediated lysis of tumor cells.