Tumor protein p53 mutant neoantigen peptide (TP53 mutant neoantigen)

TP53 mutant neoantigen peptides are short amino acid sequences derived from the proteasomal degradation of mutated tumor protein p53, which are subsequently presented on the surface of cancer cells by human leukocyte antigen (HLA) molecules (UniProt P04637). As TP53 is the most frequently mutated gene in human cancers, these neoantigens represent highly specific targets for immunotherapy because they are absent in normal tissues, minimizing the risk of systemic toxicity (Malekzadeh et al., 2019, JCI). These peptides are typically generated from hotspot mutations, such as R175H, R248Q, or R273H, which occur across various malignancies including ovarian, colorectal, and lung cancers (Hsiue et al., 2021, Science). Therapeutic strategies targeting these neoantigens include personalized cancer vaccines, such as mRNA-4157, and adoptive cell transfer using T-cell receptors (TCR-T) specifically engineered to recognize the peptide-HLA complex (Lo et al., 2017, Science). Additionally, bispecific antibodies and TCR-like antibodies are being developed to bridge T-cells to cancer cells presenting these p53-derived epitopes. The primary challenge in targeting these peptides lies in their HLA-restricted nature, meaning a specific therapy must match both the patient's mutation and their specific HLA allele. Furthermore, there is a risk of tumor immune evasion through the downregulation of antigen presentation machinery or loss of the mutant allele. Successful targeting induces a potent cytotoxic T-lymphocyte response, leading to the selective destruction of TP53-mutant tumor cells.

Other names

p53 mutant neoepitopemutant p53 peptideTP53-derived neoantigenp53-HLA complex

Therapeutic agents target the mutant peptide-HLA complex on the tumor cell surface to trigger T-cell mediated apoptosis.