Tumor protein p53-derived HLA-A*0201-restricted epitope (p53/HLA-A*0201)

The Tumor protein p53 (TP53)-derived HLA-A*0201-restricted epitope is a peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy [1]. It consists of a specific peptide fragment derived from the p53 protein, which is presented on the cell surface by the HLA-A*0201 molecule, a common MHC Class I allele [1]. Because p53 is mutated or overexpressed in over 50% of human cancers, these epitopes act as tumor-associated antigens or neoantigens that signal the presence of malignancy to the immune system [2]. Cytotoxic T lymphocytes (CTLs) recognize this complex through their T-cell receptors (TCRs), leading to the targeted destruction of the cancer cell [2]. Therapeutic interventions targeting this complex include TCR-engineered T-cell (TCR-T) therapies and cancer vaccines designed to enhance the frequency and activity of p53-specific T cells [3]. Clinical development has focused on both wild-type p53 sequences, which are overexpressed in many tumors, and specific hotspot mutations like R175H, which create highly specific neoantigens [2, 4]. A primary challenge in targeting wild-type epitopes is the potential for on-target, off-tumor toxicity in normal tissues that express basal levels of p53 [1]. Additionally, tumors may escape immune detection by downregulating HLA-A*0201 expression or through other mechanisms of the immunosuppressive tumor microenvironment [3].

Other names

p53 peptide-HLA-A*0201 complexp53/HLA-A2 complexp53(264-272)/HLA-A*0201p53-R175H/HLA-A*0201 neoantigenp53-derived pMHC

The target acts as a ligand for T-cell receptors (TCRs); therapeutic agents such as TCR-engineered T-cells or vaccines bind to or induce T-cells to recognize this complex, triggering the release of cytotoxic granules and inducing apoptosis in the target cancer cell [1, 2].