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Breakthrough Immunotherapy for Brain Cancer: Epidermal Growth Factor Receptor Variant III Chimeric Antigen Receptors

Posted Jun 30 2011 8:00pm

Description of Invention:
Scientists at the National Institutes of Health (NIH) have developed chimeric antigen receptors (CARs) with high affinity for the epidermal growth factor receptor variant III (EGFRvIII) to use as a promising immunotherapy for aggressive brain cancer (glioblastoma) as well as several other malignancies. CARs are hybrid proteins consisting of the portion of an antibody that recognizes a cancer antigen, in this case human monoclonal antibody 139 which 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.

Applications:
  • Immunotherapeutics to treat and/or prevent the recurrence of a variety of cancers that overexpress human EGFRvIII, primarily glioblastoma multiforme (GBM). About half of GBM tumor cells express the EGFRvIII antigen. Other cancers that overexpress EGFRvIII include breast, ovarian, prostate, bladder, colorectal, non-small cell lung carcinomas, and head and neck squamous cell carcinomas.
  • A personalized cancer treatment strategy for patients whose tumor cells express EGFRvIII whereby the patient’s own T cells are isolated, engineered to express the EGFRvIII specific CAR, and re-infused into the patient to attack the tumor.
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 GBM tumor cells and also in other tumor types, such as other nervous system cancers and head and neck cancers. There exist very few, if any, effective treatments for GBM, so the expected clinical benefit of an anti-EGFRvIII CAR to patients is expected to be a therapeutic breakthrough for treatment of this cancer. 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, a type of cancer with a long-felt need for breakthrough therapeutics.

Advantages:
  • EGFRvIII CAR immunotherapy is a breakthrough treatment for glioblastomas, a cancer with no other effective treatment option.
  • EGFRvIII CARs can cross the blood-brain barrier, are expected to target only tumor cells, and thus, generate fewer side effects than other brain cancer treatment approaches.
  • With the advent of Provenge®, personalized immunotherapy is becoming more widely accepted as a viable cancer treatment option.


Development Status:
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.

Inventors:
Steven A Rosenberg (NCI)
Richard A Morgan (NCI)


Patent Status:
HHS, Reference No. E-148-2011/0
US, Application No. 61/473,409 filed 08 Apr 2011


Related Technologies:
US, Application No. 61/384,931 filed 21 Sep 2010, Reference No. E-269-2010/0
US, Application No. 61/405,668 filed 22 Oct 2010, Reference No. E-236-2010/0
PCT, Application No. PCT/US2010/048701 filed 14 Sep 2010, Reference No. E-205-2009/0 which published as WO 2011/041093 on 07 Apr 2011
US, Application No. 61/247,625 filed 01 Oct 2009, Reference No. E-205-2009/0


Relevant Publication:
  1. 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”
  2. 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”
  3. Bullian SS, et al. Genetically engineered T cells to target EGFRvIII expressing glioblastoma. J Neurooncol. 2009 Sept;94(3):373-382. [ PMID: 19387557 ]
  4. Ohno M, et al. Retrovirally engineered T-cell based immunotherapy targeting type III variant epidermal growth factor receptor, a glioma-associated antigen. Cancer Sci. 2010 Dec;101(12):2518-2524. [ PMID: 20880333 ]


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
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 cell-based immunotherapies targeting EGFRvIII expressing cancers. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.


For Licensing Information Please Contact:
Samuel Bish Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: bishse@mail.nih.gov
Phone: 301-435-5282
Fax: 301-402-0220


Ref No: 2278

Updated: 07/2011

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