title: CD40 Signaling Drives Potent Cellular Immune Responses in Heterologous Cancer Vaccinations.
abstract: Antagonistic antibodies targeting coinhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited because of the insufficient induction of adaptive immune responses. Here, we describe a novel vaccination method consisting of a primary dendritic cell (DC) immunization followed by a composite vaccination, including an agonistic CD40 antibody, soluble antigen, and a TLR3 agonist, referred to as CoAT. In mice, DC/CoAT prime-boost vaccinations targeting either MHC class I or II neoantigens or tumor-associated antigens rendered up to 60% of the total T-cell population specific for a single tumor epitope. DC/CoAT induced durable and complete remissions of large subcutaneous tumors without detectable side effects. Thus, booster vaccinations with agonistic costimulatory antibodies represent an ideal means to amplify DC vaccinations and induce robust T-cell immune responses while providing maximum flexibility regarding the choice of antigen.Cancer Res; 77(8); 1918-26. ©2017 AACR.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.|Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Supot
authors.initials: S
authors.lastname: Nimanong
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
authors.forename: Dmitrij
authors.initials: D
authors.lastname: Ostroumov
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Wingerath
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Knocke
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Woller
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
authors.forename: Engin
authors.initials: E
authors.lastname: Gürlevik
authors.affiliation: Institute of Transplant Immunology, IFB-Tx, Hannover Medical School Hannover, Hannover, Germany.|DZIF, German Center for Infectious Diseases, Hannover/Braunschweig, Germany.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Falk
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Kühnel
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany. Wirth.Thomas@mh-hannover.de.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Wirth
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000819:agonists / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D016219:Immunotherapy, Adoptive / Q000379:methods; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000276:immunology; D014611:Vaccination / Q000379:methods
chemical_list: D019013:CD40 Antigens; D019496:Cancer Vaccines; D009842:Oligopeptides; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3