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Chimeric Antigen Receptors that Recognize Mesothelin for Cancer Immunotherapy

Summary
Researchers at the NCI have developed chimeric antigen receptors (CARs) with a high affinity for mesothelin to be used as an immunotherapy to treat pancreatic cancer, ovarian cancer, and mesothelioma. Cells that express CARs, most notably T cells, are highly reactive against their specific tumor antigen in an MHC-unrestricted manner to generate an immune response that promotes robust tumor cell elimination when infused into cancer patients.
NIH Reference Number
E-078-2012
Product Type
Keywords
  • CAR, immunotherapy, mesothelin, T-cells
Collaboration Opportunity
This invention is available for licensing and co-development.
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Description of Technology

Chimeric antigen receptors (CARs) with high affinity for mesothelin that can be used as an immunotherapy to treat cancers that express mesothelin, such as pancreatic cancer, ovarian cancer, and mesothelioma. The technology includes CAR constructs with one of three different mesothelin-specific antibody portions, including either the mouse-derived SS or SS1 antibody fragments or the human HN1 antibody fragment.

Mesothelin is a protein cancer antigen with limited expression on normal cells that is overexpressed by cancer cells. CARs are hybrid proteins consisting of an antibody portion that recognizes a cancer antigen, such as a mesothelin-specific antibody, fused to receptor signaling domains that serve to activate the CAR-expressing cell to kill tumor cells. Cells that express CARs, most notably T cells, are highly reactive against their specific tumor antigen in an MHC-unrestricted manner to generate an immune response that promotes robust tumor cell elimination when infused into cancer patients. Infusion of cells expressing these mesothelin-specific CARs into patients could prove to be a powerful new immunotherapeutic tool for treating various cancers that express mesothelin.

Potential Commercial Applications

• Immunotherapeutics to treat and/or prevent the reoccurrence of cancers that overexpress mesothelin.
• A personalized cancer treatment strategy for patients whose tumor cells express mesothelin.
• Tools to diagnose the presence of mesothelin-expressing tumors in patients.

Competitive Advantages

• Generates fewer side effects than other cancer treatment approaches.
• Immunotoxins containing the antibody portions of some of these CARs have shown promising results in clinical studies for cancer treatment.
• Immunotherapy is more widely accepted as a viable cancer treatment option.

Inventor(s)

Steven Rosenberg (NCI), Steven Feldman (NCI), Ira Pastan

Development Stage
Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 61/614,612, Filed 23 Mar 2012
  • Foreign Filed: Foreign Filed - Patent Application PCT/US13/28980, Filed 05 Mar 2013
  • Foreign Issued: Canada - Patent Number , Filed 22 Sep 2014
  • Foreign Filed: European - Patent Application 13717593.1, Filed 17 Sep 2014
  • Foreign Issued: Australia - Patent Number 2013235726, Issued 03 Aug 2017
  • U.S. Patent Issued: U.S. Patent Number 9359447, Issued 07 Jun 2016
Related Technologies
Therapeutic Area
Posted
Wednesday, October 11, 2017