title: Successful combined intratumoral immunotherapy of established murine mesotheliomas requires B-cell involvement.
abstract: Combination immunotherapy has resulted in a number of impressive outcomes in mouse models and clinical settings. In this study, we report that a timed triple immunotherapy (TTI) protocol using 3 agonist antibodies (anti-CD25mAb, anti-TGF-βmAb, and anti-CTLA-4mAb) produced complete clearance of established AB1 murine mesothelioma tumors. Combining all 3 agonist antibodies into a single cocktail for intratumoral injection was as effective as the TTI in tumor eradication. Cured mice showed elevated levels of tumor-specific IgG antibodies at 95 days posttreatment. Time-course studies of tumor clearance showed (1) that IgG levels were not elevated during tumor clearance and (2) that B-cell numbers were increased in the tumor-draining lymph nodes and spleens during tumor clearance. Finally, employment of B-cell knockout mice indicated a significant role for B cells in the successful eradication of the established tumors by the triple immunotherapy cocktail.
authors.affiliation: 1 School of Pathology and Laboratory Medicine (M502), Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia , Crawley, Australia .
authors.forename: Shruti
authors.initials: S
authors.lastname: Krishnan
authors.forename: Emily
authors.initials: E
authors.lastname: Bakker
authors.forename: Cassandra
authors.initials: C
authors.lastname: Lee
authors.forename: Haydn T
authors.initials: HT
authors.lastname: Kissick
authors.forename: Demelza J
authors.initials: DJ
authors.lastname: Ireland
authors.forename: Manfred W
authors.initials: MW
authors.lastname: Beilharz
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D007167:Immunotherapy; D008654:Mesothelioma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*
chemical_list: D000912:Antibodies, Neoplasm