Human leukocyte antigen A*02:01-p53 peptide complex (HLA-A2/p53)

The Human leukocyte antigen A*02:01-p53 peptide complex is a specific molecular target consisting of the MHC Class I molecule HLA-A*02:01 and a peptide fragment derived from the p53 tumor suppressor protein [1]. In many malignancies, mutations in the TP53 gene lead to the accumulation of mutant p53 protein, which is then processed and presented on the cell surface as neoantigens within the HLA-A2 binding groove [2]. This complex is absent or present at very low levels on normal cells, making it an attractive target for precision immunotherapy [3]. Therapeutic approaches primarily involve T-cell receptor (TCR) engineered T-cells or TCR-mimetic bispecific antibodies that specifically recognize the peptide-HLA interface [1, 4]. These therapies aim to redirect the patient's immune system to recognize and destroy cancer cells expressing the specific p53 mutation, such as the common R175H substitution [1]. Clinical development focuses on solid tumors where p53 mutations and HLA-A*02:01 prevalence are high, such as ovarian and colorectal cancers [2]. However, the strategy requires precise discrimination between mutant and wild-type p53 peptides to avoid systemic toxicity [3]. Sources: [1] Hsiue, E. H., et al. (2021). Science. DOI: 10.1126/science.abc8697; [2] Lo, W., et al. (2019). JCI Insight. DOI: 10.1172/jci.insight.123175; [3] Malekzadeh, P., et al. (2019). Frontiers in Immunology. DOI: 10.3389/fimmu.2019.03024; [4] Poseida Therapeutics. (2023). Pipeline Information.

Other names

HLA-A*02:01 presenting p53 epitopesp53-HLA-A2 complexp53-MHC class I complexp53-derived peptide-HLA-A*02:01 complexp53 neoantigen-HLA complex

T-cell receptor (TCR) mediated recognition and subsequent T-cell activation leading to targeted lysis of cells presenting the p53-HLA complex.