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Chimeric Antigen Receptors (CAR)-T Cells that Target the Non-Shed Portion of Mesothelin as a Therapeutic Agent

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Summary
The National Cancer Institute (NCI) developed Chimeric Antigen Receptors (CAR)-T Cells specifically targeting the unshed portion (“stalk”) of mesothelin in mesothelioma and other tumors. The NCI seeks licensing and/or co-development research collaborations to advance the development and commercialization of these inventions for immunotherapy
NIH Reference Number
E-033-2022
Product Type
Keywords
  • Antibody, Mesothelin, Mesothelioma, Cancer, Therapeutic, Diagnostic, Chimeric Antigen Receptor, CAR, Bispecific T-cell engager, BiTE, Immunotherapy, Pastan
Collaboration Opportunity
This invention is available for licensing.
Contact
Description of Technology

Mesothelin (MSLN) is an excellent target for antibody-based therapies of cancer because of its high expression in many malignancies but lack of expression on essential normal tissues. Unfortunately, a large fragment of MSLN is shed from cancer cells, causing the currently available anti-MSLN antibodies (and immunoconjugates thereof) which bind to the shed portion of MSLN to quickly lose their therapeutic effectiveness over time. Indeed, the shed portion of MSLN can act as a decoy for these antibodies, further limiting them from reaching and destroying tumor cells.

Scientists at NCI previously developed MAB15B6, an antibody that specifically binds to the unshed region of MSLN and blocks MSLN shedding. Building on this discovery, the inventors made specific modifications to CARs which utilize humanized MAB15B6.  T cells expressing these enhanced CARs are very active in blocking tumor progression in xenograph models. As a result, these CAR-T cells represent an excellent therapeutic candidate for patients who have not responded to other MSLN-targeted therapeutics.

Potential Commercial Applications
  • Treatment of MSLN-positive malignancies such as synovial sarcoma, mesothelioma, and ovarian, lung, esophageal, pancreatic and gastric cancers
  • Therapeutic Use as a targeting moiety for CARs, antibody-drug conjugates (ADCs), immunotoxins (RITs), bispecific antibodies, etc.

 

Competitive Advantages
  • The inventors have made specific improvements to immunoconjugates which utilize MAB15B6 that significantly enhance the ability of these immunoconjugates to exert a therapeutic effect
  • Specific binding to the unshed portion of MSLN allow the antibodies and CAR-T cells to maintain contact with the cancer cells for a longer duration to exert a therapeutic effect
  • More effective in blocking tumor progression compared to currently available anti-MSLN antibodies

 

Development Stage
Publications

Awuah P, et al. Reduced shedding of surface mesothelin improves efficacy of mesothelin-targeting recombinant immunotoxins.  [PMID 27196771]

Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 63/290,761, Filed 17 Dec 2021
Therapeutic Area
Posted
Tuesday, January 25, 2022