title: Mesothelin as a target for chimeric antigen receptor-modified T cells as anticancer therapy.
abstract: Mesothelin is a promising target for immune-based therapy, specifically for mesothelioma and pancreatic and ovarian cancers that have high levels of mesothelin expression. Many preclinical and clinical studies that target tumors with high mesothelin expression with antibodies, immunotoxins, antibody-drug conjugates and vaccines have shown the potential of mesothelin as a target. Studies of T cells genetically modified with chimeric antigen receptors (CAR) report significant efficacy in hematologic malignancies, and antimesothelin CAR T cells are currently being investigated in clinical studies. Here we outline the rationale for using mesothelin as a target for immunotherapy, review the clinical and preclinical studies evaluating mesothelin-directed therapies and explore the promise of CAR T cells directed against mesothelin for immunotherapy in the future.
authors.affiliation: Division of Hematologic Oncology of the University of Pennsylvania, 3400 Ciciv Center Boulevard, Perelman Center of Advanced Medicine, PA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: O'Hara
authors.affiliation: Department of Gynecologic Oncology of the University of Pennsylvania, 3400 Ciciv Center Boulevard, Perelman Center of Advanced Medicine, PA, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Stashwick
authors.affiliation: Section of Interventional Pulmonology & Thoracic Oncology of The University of Pennsylvania, 3400 Ciciv Center Boulevard, Perelman Center of Advanced Medicine, PA, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Haas
authors.affiliation: Department of Gynecologic Oncology of the University of Pennsylvania, 3400 Ciciv Center Boulevard, Perelman Center of Advanced Medicine, PA, USA.|Hospital of the University of Pennsylvania, 3400 Civic Center Boulevard, Jordan Center, Philadelphia, PA 19104, USA.
authors.forename: Janos L
authors.initials: JL
authors.lastname: Tanyi
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D002986:Clinical Trials as Topic; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive; D000090204:Mesothelin; D008654:Mesothelioma / Q000276:immunology / Q000628:therapy*; D058990:Molecular Targeted Therapy; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology* / Q000637:transplantation
chemical_list: D019496:Cancer Vaccines; D058851:GPI-Linked Proteins; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D000090204:Mesothelin
keywords: chimeric antigen receptor; immunotherapy; mesothelin; mesothelioma; ovarian cancer; pancreatic cancer