TP53 R175H mutant peptide – HLA-A*02:01 complex

The TP53 R175H mutant peptide – HLA-A*02:01 complex is a cell-surface neoantigen formed when a peptide (HMTEVVRHC) containing the R175H mutation from the tumor suppressor p53 protein is presented by the HLA-A*02:01 class I MHC molecule on tumor cells. This complex is not present in normal tissues, making it an attractive target for immunotherapies such as bispecific antibodies and engineered T cell receptors. The complex enables selective recognition and destruction of cancer cells harboring the TP53 R175H mutation. Therapeutics targeting this complex work by recruiting and activating T cells at the tumor site through molecular bridges that specifically recognize the mutant peptide/MHC complex and CD3 on T cells[1][2][3][5]. The density of the mutant complex on cancer cell surfaces is reported to be generally low, potentially limiting the effectiveness of some therapies, but high-affinity TCR-mimic antibodies and bispecific formats are being developed to overcome this challenge[5][3][1]. This target represents a paradigm for neoantigen-driven immunotherapy in cancer.

Other names

p53 R175H peptide – HLA-A2 complexMutant p53 neoantigen – HLA-A*02:01TP53 (R175H) neoepitope – HLA-A*02:01 complex

Recruitment and activation of T cells via bispecific antibodies (linking the mutant peptide–HLA complex and TCR/CD3 on T cells) to mediate tumor cell killing[1][3][5] Selective immune recognition of cancer cells presenting the mutant peptide[2][3] Mimicking T cell receptor (TCR) recognition of tumor-specific neoantigen/MHC complex