T Cell Receptors (TCRs) Specific for Mutant p53

Mutations in tumor protein p53 are expressed in a variety of human cancers such as colon, pancreatic, breast, and non-small cell lung cancer. P53 acts as a tumor suppressor by regulating cell division and DNA repair. Mutations of p53 reduce or eliminate its regulatory functions, contributing to cancer formation and progression. Novel therapeutics are needed that specifically target p53 mutations, as small molecule inhibitors lack sequence specificity.T cell receptors (TCRs) are proteins expressed on the surface of T lymphocytes that can recognize peptide antigens from infected and malignant cells in the context of human leukocyte antigen (HLA) molecules with exquisite specificity. Subsequent T cell activation leads to an immune response which aims to eliminate abnormal cells. TCRs may be further engineered to recognize specific tumor antigens. Adoptive transfer of these tumor antigen-specific TCR-engineered T cells into patients has been demonstrated as a promising cancer treatment strategy.  Researchers at the National Cancer Institute (NCI) identified T-cell receptors (TCRs) targeting a specific mutation in the p53 tumor suppressor, R175H, in the context of HLA-DRB1*13:01. The p53-R175H “hotspot” mutation occurs in ~4.5% of all cancers, and as such, is an attractive target for adoptive T cell immunotherapy. Normal tissue does not express the mutated p53 protein. Therefore, these TCRs are expected to specifically eliminate human cancer cells that express both the approp...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research