TP53 mutant neoantigen peptides presented by Major Histocompatibility Complex class I (TP53-neoantigen-MHC-I)

TP53 mutant neoantigen peptides presented by MHC class I are highly specific tumor antigens derived from somatic mutations in the TP53 tumor suppressor gene. TP53 is the most frequently mutated gene in human cancers, and certain 'hotspot' mutations result in the production of stable mutant proteins that are processed and presented as neoepitopes on the cell surface via the Major Histocompatibility Complex (MHC) class I pathway (Hsiue et al., 2021, Science). Because these mutant peptides are not found in normal tissues, they serve as ideal targets for immunotherapy, allowing the immune system to distinguish between malignant and healthy cells (Lo et al., 2020, JCI). Therapeutic approaches targeting these complexes include T-cell receptor (TCR) engineered T cells, bispecific antibodies (T-cell engagers), and neoantigen-based vaccines (Malekzadeh et al., 2019, JCI). These therapies aim to harness the precision of the cellular immune response to eliminate TP53-mutant tumor cells while minimizing damage to normal tissues that express only wild-type p53. The clinical success of these targets is highly dependent on the patient's specific HLA haplotype and the presence of the corresponding TP53 mutation.

Other names

p53 mutant neoantigen-HLA complexMutant p53-MHC class I complexTP53 hotspot mutation neoantigensp53-derived neoepitopes

Induction of T-cell mediated cytotoxicity through the specific recognition of mutant p53 peptides displayed on the tumor cell surface by MHC class I molecules.