T-cell receptor recognizing p53 peptide–MHC complexes (p53-specific TCR)

The T-cell receptor (TCR) recognizing p53 peptide–MHC complexes is a specialized immune receptor engineered or isolated to target one of the most frequently mutated proteins in human cancer. The p53 protein, often called the guardian of the genome, typically functions as a tumor suppressor; however, mutations in the TP53 gene lead to the presentation of unique neoantigens or overexpressed wild-type peptides on the cell surface via Major Histocompatibility Complex (MHC) molecules. By utilizing TCR-engineered T-cell (TCR-T) therapy, clinicians can redirect a patient's immune system to specifically identify and eliminate cells displaying these p53 fragments. This approach is particularly valuable because it allows the targeting of intracellular oncogenic drivers that are inaccessible to traditional antibody-based therapies. Current therapeutic development focuses on matching specific TCRs to common HLA types, such as HLA-A*02:01, to treat a wide range of solid tumors including lung, breast, and colorectal cancers. While promising, the therapy requires careful monitoring for systemic inflammatory responses and potential cross-reactivity with normal tissues expressing low levels of p53.

Other names

p53-reactive T-cell receptoranti-p53 TCRp53-targeted T-cell receptorp53-MHC-specific TCR

Engineered T-cells expressing the specific TCR recognize and bind to p53-derived peptides presented by Major Histocompatibility Complex (MHC) molecules on the surface of tumor cells, triggering T-cell activation, cytokine secretion, and direct cytotoxic killing of the cancer cell.