title: CD40-activated B cells induce anti-tumor immunity in vivo.
abstract: The introduction of checkpoint inhibitors represents a major advance in cancer immunotherapy. Some studies on checkpoint inhibition demonstrate that combinatorial immunotherapies with secondary drivers of anti-tumor immunity provide beneficial effects for patients that do not show a strong endogenous immune response. CD40-activated B cells (CD40B cells) are potent antigen presenting cells by activating and expanding naïve and memory CD4+ and CD8+ and homing to the secondary lymphoid organs. In contrast to dendritic cells, the generation of highly pure CD40B cells is simple and time efficient and they can be expanded almost limitlessly from small blood samples of cancer patients. Here, we show that the vaccination with antigen-loaded CD40B cells induces a specific T-cell response in vivo comparable to that of dendritic cells. Moreover, we identify vaccination parameters, including injection route, cell dose and vaccination repetitions to optimize immunization and demonstrate that application of CD40B cells is safe in terms of toxicity in the recipient. We furthermore show that preventive immunization of tumor-bearing mice with tumor antigen-pulsed CD40B cells induces a protective anti-tumor immunity against B16.F10 melanomas and E.G7 lymphomas leading to reduced tumor growth. These results and our straightforward method of CD40B-cell generation underline the potential of CD40B cells for cancer immunotherapy.
authors.affiliation: Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wennhold
authors.affiliation: Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Tanja M
authors.initials: TM
authors.lastname: Weber
authors.affiliation: Department of Hematology, Vall d'Hebron University Hospital, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Nela
authors.initials: N
authors.lastname: Klein-Gonzalez
authors.affiliation: Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Thelen
authors.affiliation: Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Garcia-Marquez
authors.affiliation: Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Geothy
authors.initials: G
authors.lastname: Chakupurakal
authors.affiliation: Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Fiedler
authors.affiliation: Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.|Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany.
authors.forename: Hans A
authors.initials: HA
authors.lastname: Schlösser
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Rieke
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.|Laboratory for Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research Cologne, Cologne, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Theurich
authors.affiliation: Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Shimabukuro-Vornhagen
authors.affiliation: Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: von Bergwelt-Baildon
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D023041:Xenograft Model Antitumor Assays
chemical_list: D000951:Antigens, Neoplasm; D019013:CD40 Antigens; D019496:Cancer Vaccines
keywords: B cell; CD40-activated B cells; antigen presentation; cancer immunotherapy; cellular adjuvant