title: Novel Antibody Therapeutics Targeting Mesothelin In Solid Tumors.
abstract: Monoclonal antibodies have become attractive clinical anti-cancer 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Bayer Pharmaceuticals, Biologics Research, San Francisco, CA,USA.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhao
authors.affiliation: Bayer Pharmaceuticals, Biologics Research, San Francisco, CA,USA.
authors.forename: Babu
authors.initials: B
authors.lastname: Subramanyam
authors.affiliation: Clinical Sciences, Whippany, NJ,USA.
authors.forename: Nenad
authors.initials: N
authors.lastname: Sarapa
authors.affiliation: Therapeutic Research Oncology, Berlin,Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Golfier
authors.affiliation: Bayer Pharmaceuticals, Biologics Research, San Francisco, CA,USA.
authors.forename: Harald
authors.initials: H
authors.lastname: Dinter
keywords: 7D9-MMAE; Amatuximab; Anetumab ravtansine; Antibody (Ab); BMS-986148; DM1 or DM4: maytansinoid tubulin inhibitors; DMOT4039A; MDX-1204; Monomethyl auristatin E (MMAE); RG7787; SS1P; antibody-drug conjugate (ADC); antigen; cancer; chimeric monoclonal antibody; mesothelin; recombinant immunotoxin (RIT); unconjugated antibody