T cell Receptors Which Recognize Mutated EGFR

Epidermal growth factor receptor (EGFR) is a transmembrane protein involved in cell growth and proliferation. Mutations in this protein can lead to overexpression, causing several types of cancer; notably, non-small cell lung cancer (NSCLC). For example, mutations in EGFR are found in up to 50% of NSCLC patients and the E746-A750 deletion accounts for 30-40% of such EGFR mutations. Currently, there are no available therapeutics that specifically target the E746-A750 deletion. 

Researchers at the National Cancer Institute (NCI) have isolated T cells that recognize the EGFR E746-A750 deletion. Retroviral transfer of the TCR genes conferred recognition of tumor cell lines with EGFR E746-A750 deletion in the context of HLA DPA1*02:01 and DPB1*01:01. These HLAs exists in about 10% of Caucasians and 50% African Americans, respectively, in the US. This discovery allows for the specific elimination of tumor cells with E746-A750 deletion mutation present in a significant portion of the more than 222,500 NSCLC patients. 

The National Cancer Institute, Surgery Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these novel, EGFR mutation-reactive TCRs.

Competitive Advantages:

• First T cell receptor that can kill tumors by targeting the EGFR E746-A750 deletion
• EGFR mutations common in non-small cell lung cancer patients

Commercial Applications:

• Significant number of lung cancer patients may benefit from this receptor
• Use of the TCRs in chimeric proteins for research purposes in cancers with mutated EGFR