Breakthrough Immunotherapy for Brain Cancer


Chimeric antigen receptors (CARs) with high affinity for the epidermal growth factor receptor variant III (EGFRvIII) for use as an immunotherapy for glioblastoma and other cancers. CARs are hybrid proteins consisting of the portion of an antibody that recognizes a cancer antigen, in this case human monoclonal antibody 139. This Mab recognizes EGFRvIII, fused to protein signaling domains that serve to activate the CAR-expressing cell. Human cells that express CARs, most notably T cells, can recognize specific tumor antigens in an MHC-unrestricted manner with high reactivity and mediate an immune response that promotes robust tumor cell elimination.

EGFRvIII is a rare antigen in that is highly expressed by tumor cells, but not expressed by other cells in the body. This cancer antigen is expressed on nearly 50% of glioblastoma multiforme tumor cells and other tumor types, such as other nervous system and head and neck cancers. There exist very few, if any, effective treatments for glioblastoma multiforme.

These CARs are expected to combine high affinity recognition of EGFRvIII provided by the antibody portion with the target cell killing activity of cytotoxic T cells. Infusion of these EGFRvIII-specific CARs into patients could prove to be a powerful new immunotherapeutic tool for treating brain cancers.

Potential Commercial Applications: Competitive Advantages:
  • Immunotherapeutics to treat and/or prevent the recurrence of cancers that overexpress human EGFRvIII, such as glioblastoma multiforme
  • Personalized cancer treatment strategy for patients whose tumor cells express EGFRvIII
 
  • Breakthrough treatment for glioblastomas
  • Can cross the blood-brain barrier and generate fewer side effects than other treatment approaches


Development Stage:
This technology could soon be ready for clinical development. A clinical protocol to utilize an EGFRvIII CAR to treat GBM is currently under review at NIH.

Related Invention(s):
E-205-2009-0
E-269-2010-0


Inventors:

Steven Rosenberg (NCI)  ➽ more inventions...

Richard Morgan (NCI)  ➽ more inventions...


Intellectual Property:
U.S. Pat: 9,624,306 issued 2017-04-18
U.S. Pat: 9,266,960 issued 2016-02-23
PCT Application No. PCT/US12/29861
US Application No. 14/110,189
US Application No. 15/448,707
Available as a Research Tool only.

Publications:
Weber R, et al. US Patent No. 7,628,986 issued December 8, 2009 entitled “Antibodies Directed to the Deletion Mutants of Epidermal Growth Factor Receptor and Uses Thereof” PMID 19387557
Carter BS, et al. US Patent Application No. 12/444,090 filed April 2, 2009 entitled “Chimeric T-Cell Receptors and T-Cells Targeting EGFRvIII on Tumors” PMID 20880333
Bullian SS, et al.
Ohno M, et al.

Licensing Contact:
Andrew Burke, Ph.D.
Email: burkear@mail.nih.gov
Phone: 240-276-5484

OTT Reference No: E-148-2011-0
Updated: Nov 7, 2018