title: An In Vitro Model That Predicts the Therapeutic Efficacy of Immunomodulatory Antibodies.
abstract: Immunomodulatory monoclonal antibodies (mAbs) have efficacy in patients with advanced cancer and are the focus of intensive research. However, cures are infrequent and responses vary among tumor types and among subjects with the same tumor. An in vitro test would be valuable to determine the most effective mAb combination for a given case and to evaluate novel agents. Toward this goal, we investigated the ability of various mAb combinations to generate a tumor-destructive immune response in vitro in the presence of lymphoid cells from mice with established TC1 lung carcinoma, B16 melanoma, or SW1 melanoma. The data strongly correlate (r=0.9, 0.89, and 0.91, respectively) with the therapeutic efficacy of the respective mAb combinations. Both in vivo and in vitro, tumor destruction was associated with a shift from a Th2 to a Th1 response and included a dramatic increase of long-term memory cells. A combination of mAbs to CD137/PD-1/CTLA4/CD19 was most efficacious.
authors.affiliation: Department of Pathology, Harborview Medical Center, University of Washington, Seattle, WA.
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.forename: Yuen Yee
authors.initials: YY
authors.lastname: Yip
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Hellstrom
authors.forename: Karl Erik
authors.initials: KE
authors.lastname: Hellstrom
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006801:Humans; D007156:Immunologic Memory; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9