Humanized 40H3 Antibody

Summary:

The NCI seeks research co-development partners or licensees for monoclonal antibodies that specifically target cancer-expressed EGFR.

Description of Technology:

Epidermal growth factor receptor (EGFR) is a well-known oncogenic driver in lung cancer, head and neck cancer, glioblastoma multiforme (GBM) and other cancers. NCI inventors have previously isolated a mouse monoclonal antibody that binds to the human EGFRvIII – but not wildtype EGFR known as the 40H3 antibody (NCI Ref: E-103-2019). To improve the 40H3 antibody’s suitability for the clinic, the inventors humanized the antibody through the generation of multiple variants with distinct sequences. The inventors produced about 14 humanized candidates of the 40H3 antibody. Significantly, CAR Ts using one of the antibodies (A10) showed potent killing of cancer cells in various pre-clinical models overexpressing EGFR. The pre-clinical results obtained to date suggest that the A10 antibody is a promising candidate for development as various therapeutics for the treatment of EGFRvIII-expressing cancers.

Potential Commercial Applications:

• Cancer therapeutic against numerous EGFRvIII-expressing tumor types – including, but not limited to, lung cancer, head and neck cancer and GBM.
• Therapeutic applications of the unconjugated antibodies
• Use of the unconjugated antibodies as a targeting moiety in antibody-drug conjugates (ADCs), radio-immunotherapies (RITs) and chimeric antigen receptors (CARs)
• Diagnostic agent for detection and monitoring levels of EGFRvIII-expressing cancers

Competitive Advantages:

• Less non-specific cell killing using humanized EGFRvIII antibodies with high EGFRvIII binding specificity will result in fewer and lower grade potential side effects
• Therapeutic development against various common and rare cancers represent many paths to market and out-licensing opportunities
• CAR Ts using the A10 antibody are available for immediate testing
• A10 binding EGFR when over-expressed from amplified EGFR is specific to various cancers