Human leukocyte antigen A*02:01-presented tumor-associated peptide complex (HLA-A*02:01/peptide)

The Human leukocyte antigen A*02:01-presented tumor-associated peptide complex is a molecular assembly consisting of a specific intracellularly derived peptide fragment bound to the HLA-A*02:01 Class I Major Histocompatibility Complex (MHC) molecule. This complex is expressed on the surface of tumor cells, serving as a molecular barcode that signals the presence of aberrant or overexpressed proteins to the immune system (PMID: 30635554). HLA-A*02:01 is one of the most prevalent HLA alleles in human populations, particularly in Caucasians, making it a primary focus for the development of TCR-based immunotherapies (PMID: 11167777). Therapeutic agents such as TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers are designed to recognize these specific peptide-MHC (pMHC) complexes with high affinity and specificity (PMID: 34554482). By targeting these complexes, drugs can direct the cytotoxic activity of T-cells toward tumor cells that might otherwise evade detection by the innate immune system or traditional antibody-based therapies. However, the clinical application of these therapies requires precise patient selection based on HLA typing and the confirmation of target antigen expression to ensure efficacy and minimize the risk of cross-reactivity with similar peptides in healthy tissues (PMID: 38537575). This target class is unique because it allows for the therapeutic targeting of intracellular proteins, which comprise the majority of the proteome but are inaccessible to standard monoclonal antibodies.

Other names

HLA-A2-restricted tumor antigenpMHC complexHLA-A*02:01-peptide complexMHC-I/peptide complexpHLA-A*02:01HLA-A*02:01-presented tumor-associated antigen

Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-mimetic antibodies to induce T-cell mediated cytotoxicity against tumor cells.