Tumor protein p53 – Human leukocyte antigen A2 peptide complex (p53-HLA-A2 complex)

The Tumor protein p53 – Human leukocyte antigen A2 (p53-HLA-A2) peptide complex is a molecular assembly where a peptide fragment derived from the p53 protein is presented on the cell surface by the Major Histocompatibility Complex (MHC) Class I molecule HLA-A*02:01 (1.3.1, 1.3.3). In many cancers, the TP53 gene is mutated, creating neoantigens like the R175H mutation, or the wild-type protein is overexpressed, leading to the presentation of these peptides as targets for the immune system (1.1.1, 1.3.4). This complex is a critical target for advanced immunotherapies, including T-cell receptor (TCR) engineered T-cells and bispecific T-cell engagers (BiTEs), which are designed to recognize the specific structural interface of the peptide and the HLA molecule (1.3.1, 1.4.1). By targeting this complex, these therapies aim to redirect cytotoxic T-cells to selectively eliminate malignant cells while sparing healthy tissues (1.3.3, 1.4.2). However, therapeutic development faces challenges such as the extremely low density of these complexes on the tumor cell surface and the risk of off-target toxicity if the therapy cross-reacts with similar peptides in normal cells (1.3.1, 1.4.3). Clinical candidates like CLSP-1025 are currently being investigated for their potential to treat solid tumors harboring specific p53 mutations (1.4.1).

Other names

p53-MHC complexp53-HLA-A*02:01 complexp53 neoantigen-HLA complexp53(R175H)-HLA-A2 complexp53(168-176)-HLA-A2 complex

T-cell mediated cytotoxicity through TCR-mediated recognition or bispecific T-cell engagement