Tumor protein p53 R175H mutant peptide presented by HLA-A*02:01 (p53-R175H/HLA-A*02:01)

The TP53 R175H mutant peptide presented by HLA-A*02:01 is a prominent cancer neoantigen resulting from a common 'hotspot' mutation in the tumor suppressor protein p53. In many cancers, the R175H mutation leads to the loss of wild-type p53 function and the gain of oncogenic properties, with the resulting mutant protein being overexpressed and processed into peptides. One specific 9-amino acid peptide (HMTEVVRHC) containing the R175H substitution is presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*02:01. Because this specific peptide-HLA complex is absent on healthy cells, it serves as a highly specific target for immunotherapy, including T-cell receptor (TCR)-engineered T-cells and bispecific antibodies. Therapeutic strategies like JNJ-78306358 aim to redirect the immune system to recognize and eliminate cells harboring this mutation. This target is particularly relevant in solid tumors such as ovarian, colorectal, and pancreatic cancers where TP53 mutations are prevalent.

Other names

p53 R175H neoantigenp53-R175H/MHC complexTP53 R175H/HLA-A*02:01 complexp53 R175H peptide-HLA complexHMBD-002 target

T-cell engagement via bispecific antibodies or T-cell receptor (TCR) engineered T-cells that specifically recognize the mutant peptide-HLA complex on the surface of cancer cells, leading to targeted cell lysis.