Patient-specific tumor-associated peptide–HLA-A*02:01 complex (pHLA-A*02:01)

Patient-specific tumor-associated peptide–HLA-A*02:01 complexes are molecular assemblies consisting of a tumor-derived peptide fragment bound to the Human Leukocyte Antigen (HLA) A*02:01 molecule. These complexes are presented on the surface of malignant cells and serve as the primary recognition signal for the cellular immune system, specifically CD8+ cytotoxic T lymphocytes (PMID: 30612389). In modern oncology, these complexes are utilized as highly specific therapeutic targets for personalized immunotherapies, including TCR-engineered T-cells (TCR-T), bispecific T-cell engagers, and neoantigen vaccines (PMID: 28700575). For example, the drug Tebentafusp targets a gp100 peptide presented by HLA-A*02:01 to treat uveal melanoma (PMID: 34551229). The therapeutic efficacy of targeting these complexes depends on the stable presentation of the peptide and the presence of the HLA-A*02:01 allele, which is the most common HLA-A allele in Caucasian populations. However, challenges such as tumor-mediated HLA downregulation and the risk of lethal cross-reactivity with healthy tissue peptides remain significant hurdles in drug development (PMID: 38531968).

Other names

Neoantigen-HLA-A*02:01 complexTumor-specific antigen-HLA-A*02:01 complexpMHC-A*02:01 complexTumor-associated antigen-HLA-A*02:01 complex

Recognition by engineered T-cell receptors (TCRs), TCR-like antibodies, or bispecific T-cell engagers (BiTEs) to trigger cytotoxic T-lymphocyte (CTL) activation and targeted lysis of tumor cells.