T Cell Receptors Targeting p53 Hotspot Mutations and Methods of Isolating the Same

Mutations in Tumor Protein P53 (p53) are expressed in a variety of human cancers such as cholangiocarcinoma, melanoma, colon cancer, rectal cancer, ovarian cancer, endometrial cancer, non-small cell lung cancer (NSCLC), glioblastoma, uterine cervical cancer, head and neck cancer, breast cancer, pancreatic cancer, and bladder cancer. The p53 protein is involved in determining whether DNA is repaired or the damaged cell undergoes apoptosis – thus acting as a tumor suppressor by regulating cell division. Mutations in the p53 protein can reduce or eliminate its tumor suppressor function or interfere with wild type p53 in a dominant negative fashion. Furthermore, novel therapeutics are needed that specifically target p53 mutations, as small molecules lack specificity for the mutated sequences.Researchers at the National Cancer Institute (NCI) identified a collection of novel T-cell receptors (TCRs) targeting defined “hotspot” mutations in the p53 tumor suppressor. The same p53 mutations frequently occur; ~30% of the p53 missense mutations, at the following residues: R175H, Y220C, G245D, G245S, R248L, R248Q, R248W, R249S, R273C, R273L, R273H and R282W. Therefore, p53 mutations are attractive as targets for T CR gene-engineered T cell therapy. This discovery allows for the specific elimination of tumor cells with p53 mutations present in a diverse group of cancer patients. Furthermore, scientists at the NCI have developed a method of identifying T cells reactive to mutations i...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research