Monoclonal Antibodies and Immunoconjugates Directed to the Non-ShedPortion (“Stalk”) of Mesothelin are Excellent Candidates for Developing Therapeutic Agents

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.