p53-specific MHC class II-restricted T-cell receptor (p53-TCR (MHC II))

The p53-specific MHC class II-restricted T-cell receptor is a specialized antigen receptor used in cancer immunotherapy to recognize peptides derived from the p53 tumor suppressor protein. While p53 is primarily an intracellular protein, its degradation products are presented on the cell surface by MHC Class II molecules, particularly in tumor cells where p53 is mutated or overexpressed. These TCRs, typically expressed on CD4+ T cells, are engineered to bind with high affinity to specific p53 "hotspot" mutations, such as R175H or Y220C, which are common across various epithelial cancers. In therapeutic applications, patient T cells are genetically modified to express these TCRs (TCR-T therapy) to orchestrate a potent anti-tumor immune response. Upon recognition of the p53-MHC II complex, these T cells secrete pro-inflammatory cytokines like interferon-gamma and TNF-alpha, which can directly inhibit tumor growth and recruit other immune effectors, such as CD8+ cytotoxic T cells. Clinical development of these TCRs aims to provide "off-the-shelf" or personalized treatments for patients with advanced solid tumors and hematologic malignancies that harbor p53 mutations.

Other names

p53-specific MHC class II-restricted T-cell receptorp53-specific CD4+ T-cell receptorMHC class II-restricted p53-specific TCRp53-reactive CD4+ TCRHLA-DR-restricted p53 TCRp53 neoantigen-specific TCR

Adoptive transfer of T cells engineered to express the TCR, which specifically recognize p53-derived peptides presented by MHC Class II molecules on tumor cells or antigen-presenting cells, leading to T-cell activation, cytokine release, and anti-tumor effector functions.