Tumor protein p53 peptide-HLA-A*02:01 complex (p53/HLA-A*02:01)

The p53/HLA-A*02:01 complex is a peptide-major histocompatibility complex (pMHC) presented on the surface of cancer cells, serving as a critical target for neoantigen-based immunotherapy. It consists of a proteolytic fragment of the tumor protein p53—often containing a common 'hotspot' mutation like R175H—bound to the cleft of the HLA-A*02:01 molecule (Hsiue et al., Science, 2021). Because p53 is the most frequently mutated gene in human cancer, these complexes represent highly specific tumor markers that are absent or minimally present on normal tissues. Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cells and bispecific T-cell engagers (BiTEs) designed to recognize the unique structural interface of the peptide and the HLA molecule (Lo et al., Nature Medicine, 2020). The primary clinical goal is to harness the precision of the adaptive immune system to eliminate p53-mutant malignant cells while avoiding systemic toxicity. However, the low copy number of these complexes on the cell surface requires highly potent and sensitive therapeutic agents.

Other names

p53-MHC complexp53-HLA-A2 complexp53 neoantigen-HLA complexp53-derived peptide-MHC Class I complexTP53/HLA-A*02:01

Recognition of the specific p53-derived peptide presented by HLA-A*02:01 by engineered T-cell receptors (TCRs) or bispecific antibodies, leading to T-cell recruitment and cytotoxic lysis of the tumor cell.