Background: Monoclonal antibodies have become attractive clinical anticancer
drugs in the last 3 decades due to their targeting specificity and suitable pharmacokinetic
properties. Mesothelin is a tumor-associated antigen with limited expression
in normal tissues. It is frequently over-expressed on the cell membrane of a
number of epithelial malignancies (e.g. mesothelioma, pancreatic, ovarian, lung, triple
negative breast and gastric cancers).
Methods: Mesothelin is validated as a suitable antibody target for cancer therapy. A
number of novel antibody therapeutics targeting mesothelin in development are compared
and their mechanisms of action are also discussed. Both basic science and
clinical data are provided to give a complete veiw of how an agent is developed from
bench to bedside.
Results: Novel antibody therapeutics, including unconjugated monoclonal antibodies, recombinant immunotoxins
and antibody-drug conjugates, targeting mesothelin exert anti-tumor activities by different mechanisms
of action. Based on the convincing preclinical data generated with these molecules, the antibody therapeutics
have been brought into early clinical evaluation where initial promising results were obtained.
Conclusion: These antibody therapeutics directed against mesothelin are expected to have different
safety profiles, based on their different mechanism of action. Further clinical development will reveal
which of these molecules shows the best efficacy and widest therapeutic window and thus is best suited
to bring benefit to the patients.
Keywords: Antibody (Ab), antigen, mesothelin, cancer, unconjugated antibody, chimeric monoclonal antibody, recombinant
immunotoxin (RIT), antibody-drug conjugate (ADC), Amatuximab, SS1P, RG7787, Anetumab ravtansine, DM1 or DM4: maytansinoid
tubulin inhibitors, Monomethyl auristatin E (MMAE), 7D9-MMAE, DMOT4039A, MDX-1204, BMS-986148.
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