Mutant tumor protein p53 (p53) neoantigen-HLA class I complex (mut-p53/HLA-I)

Mutant tumor protein p53 (p53) neoantigen-HLA class I complexes represent a highly specific class of cancer targets derived from the most frequently mutated gene in human malignancies (Lo et al., 2020). In cancer cells, missense mutations in the TP53 gene result in the production of altered p53 proteins, which are subsequently degraded by the proteasome into mutant peptide fragments. These neoantigen peptides are then loaded onto Human Leukocyte Antigen (HLA) class I molecules and transported to the cell surface for presentation to the immune system (Malekzadeh et al., 2019). Because these specific mutant sequences are not present in the germline, they function as "true" neoantigens, providing a window for therapeutic intervention with minimal risk of targeting healthy tissues (Hsiue et al., 2021). Engineered autologous T-cell receptor (TCR) therapies utilize patient-derived T cells modified to express high-affinity TCRs that specifically bind to these mutant p53-HLA complexes. This interaction triggers T-cell activation, leading to the selective lysis of tumor cells expressing the specific p53 mutation. Current clinical strategies focus on targeting common "hotspot" mutations, such as R175H or R273H, in the context of prevalent HLA alleles like HLA-A*02:01 (Hsiue et al., 2021).

Other names

p53 neoepitopemutant p53 peptide-MHC complexTP53 neoantigenp53-HLA complexmut-p53/MHC-I

T-cell receptor-mediated recognition of the mutant peptide-HLA complex leading to cytotoxic T-lymphocyte activation and tumor cell apoptosis (Malekzadeh et al., 2019).