T Cell Receptors Targeting EGFR L858R mutation on HLA-A*11:01+ Tumors for Use as Research Tools

Tumor-specific mutated proteins can create neoepitopes, mutation-derived antigens that distinguish tumor cells from healthy cells, which are attractive targets for adoptive cell therapies. However, the process of precisely identifying the neoepitopes to target is complex and challenging. One method to identify such neoepitopes is Mass Spectrometry (MS) when used in conjunction with elution of peptides bound to a specific Human Leukocyte Antigen (HLA) allele. Using MS in this context can demonstrate which oncogene derived neoepitopes are presented by common HLA alleles, and can provide the data necessary to rapidly develop TCRs against the desired antigens. 

Using the MS approach, inventors at the National Cancer Institute (NCI) have identified neoepitopes derived from a mutated isoform of Epithelial Growth Factor Receptor (EGFR) presented by HLA A*11:01 across multiple biological replicates. From this MS data, the inventors were able to successfully isolate murine TCRs that specifically recognize HLA A*11:01 restricted neoepitopes targeting EGFR L858R. According to various cancer genome databases, EGFR L858R is highly prevalent in lung adenocarcinoma, non-small cell lung carcinoma, and nonsquamous non-small cell lung carcinoma, making this driver mutation an excellent target to develop off-the-shelf cellular therapies. While the clinical potential of these TCRs has not been explored, they are valuable research materials to identify HLA-A*11:01 EGFR L858R reactive T cells in various sources including patients and animal models.

The Surgery Branch seeks licensees for research use of these TCRs targeting EGFR L858R mutation. 

Potential Commercial Applications:

• Research use
• In vitro diagnostic use
• The TCRs may be used as positive controls to identify HLA-A*11:01 EGFR L858R reactive T cells from different sources such as patients or animal models

Competitive Advantages:

• TCRs recognize the common EGFR L858R driver mutation in the context of HLA-A*11:01 
• EGFR mutations are highly prevalent in lung cancers, especially lung adenocarcinoma, non-small cell lung cancer and non-squamous non-small cell lung cancer
• The prevalence of EGFR L858R substitutions, relative to the overall EGFR mutation population, ranges from 27.7% to 41.1% in non-small cell lung cancer patients
• HLA-A*11:01 allele frequency is particularly high (up to 60%) in Asian and Oceanian populations
• This research has validated the effectiveness of using mass spectrometry to detect amino acid sequences on specific HLA complexes