title: Mesothelin Immunotherapy for Cancer: Ready for Prime Time?
abstract: Mesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable. Several antibody-based therapeutic agents as well as vaccine and T-cell therapies directed at mesothelin are undergoing clinical evaluation. These include antimesothelin immunotoxins (SS1P, RG7787/LMB-100), chimeric antimesothelin antibody (amatuximab), mesothelin-directed antibody drug conjugates (anetumab ravtansine, DMOT4039A, BMS-986148), live attenuated Listeria monocytogenes-expressing mesothelin (CRS-207, JNJ-64041757), and chimeric antigen receptor T-cell therapies. Two antimesothelin agents are currently in multicenter clinical registration trials for malignant mesothelioma: amatuximab in the first-line setting and anetumab ravtansine as second-line therapy. Phase II randomized clinical trials of CRS-207 as a boosting agent and in combination with immune checkpoint inhibition for pancreatic cancer are nearing completion. These ongoing studies will define the utility of mesothelin immunotherapy for treating cancer.
authors.affiliation: Raffit Hassan, Anish Thomas, Christine Alewine, and Ira Pastan, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda; and Dung T. Le and Elizabeth M. Jaffee, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD.
authors.forename: Raffit
authors.initials: R
authors.lastname: Hassan
authors.affiliation: Raffit Hassan, Anish Thomas, Christine Alewine, and Ira Pastan, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda; and Dung T. Le and Elizabeth M. Jaffee, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD.
authors.forename: Anish
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Raffit Hassan, Anish Thomas, Christine Alewine, and Ira Pastan, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda; and Dung T. Le and Elizabeth M. Jaffee, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD.
authors.forename: Christine
authors.initials: C
authors.lastname: Alewine
authors.affiliation: Raffit Hassan, Anish Thomas, Christine Alewine, and Ira Pastan, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda; and Dung T. Le and Elizabeth M. Jaffee, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD.
authors.forename: Dung T
authors.initials: DT
authors.lastname: Le
authors.affiliation: Raffit Hassan, Anish Thomas, Christine Alewine, and Ira Pastan, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda; and Dung T. Le and Elizabeth M. Jaffee, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Jaffee
authors.affiliation: Raffit Hassan, Anish Thomas, Christine Alewine, and Ira Pastan, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda; and Dung T. Le and Elizabeth M. Jaffee, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD.
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D058851:GPI-Linked Proteins / Q000187:drug effects*; D006801:Humans; D018796:Immunoconjugates; D007167:Immunotherapy / Q000379:methods*; D008453:Maytansine / Q000031:analogs & derivatives; D000090204:Mesothelin; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D058851:GPI-Linked Proteins; D018796:Immunoconjugates; D008453:Maytansine; C526187:amatuximab; D000090204:Mesothelin; C000595240:anetumab ravtansine