Human mesothelin is overexpressed by various cancers such as synovial sarcoma, mesothelioma, and ovarian, lung, esophageal, and gastric cancers. This selective expression on certain cancers suggests that mesothelin is an excellent target for anticancer therapeutics. However, a large fragment (“the shed portion”) of mesothelin is constantly shed from cells, and all current anti-mesothelin antibodies bind to the shed portion. As a result, the therapeutic efficacy of these antibodies has been low because they are unable to exert their therapeutic effect on the cell before their binding region is shed.
Fortunately, a piece (“the stalk”) of mesothelin remains attached to the cell surface after shedding. Since antibodies to the stalk would remain bound to diseased cells, they can be more effective in killing cancer cells than currently available anti-mesothelin antibodies. Scientists at the National Cancer Institute (NCI) have invented antibodies that specifically recognize and bind to the stalk of human mesothelin with high affinity. These antibodies represent excellent candidates for development of therapeutic agents and are available for licensing and/or co-development opportunities.
- Therapeutic Uses
- As an unconjugated antibody
- As a targeting moiety for CARs, antibody-drug conjugates (ADC), immunotoxins, bispecific antibodies, etc.
- Diagnostic agent for detection and monitoring levels of mesothelin-expressing cancer cells
- This is the only antibody that binds to the stalk portion of mesothelin, allowing the antibody to remain attached to the cell to exert a therapeutic effect
- Specific binding to cancer cells allows selective killing, potentially limiting drug side effects and improving patient quality of life
Awuah et al., Reduced Shedding of Surface Mesothelin Improves Efficacy of Mesothelin-Targeting Recombinant Immunotoxins. [PMID 27196771]
- U.S. Patent Filed: U.S. Patent Application Number PCT/US2018/033236