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CD40-activated B cells induce anti-tumor immunity in vivo

2016; Impact Journals LLC; Volume: 8; Issue: 17 Linguagem: Inglês

10.18632/oncotarget.7720

1949-2553

Kerstin Wennhold, Tanja Weber, Nela Klein-González, Martin Thelen, María A. García-Márquez, Geothy Chakupurakal, Anne Fiedler, Hans Schlößer, Rieke Fischer, Sebastian Theurich, Alexander Shimabukuro‐Vornhagen, Michael von Bergwelt‐Baildon,

CAR-T cell therapy research

// Kerstin Wennhold 1, * , Tanja M. Weber 1, * , Nela Klein-Gonzalez 2 , Martin Thelen 1 , Maria Garcia-Marquez 1 , Geothy Chakupurakal 1 , Anne Fiedler 1 , Hans A. Schlösser 1, 3 , Rieke Fischer 4 , Sebastian Theurich 1, 5 , Alexander Shimabukuro-Vornhagen 1, * , Michael von Bergwelt-Baildon 1, * 1 Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany 2 Department of Hematology, Vall d'Hebron University Hospital, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain 3 Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany 4 Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany 5 Laboratory for Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research Cologne, Cologne, Germany * These authors have contributed equally to this work Correspondence to: Kerstin Wennhold, e-mail: Kerstin.wennhold@uk-koeln.de Keywords: cellular adjuvant, CD40-activated B cells, cancer immunotherapy, antigen presentation, B cell Received: December 15, 2015 Accepted: January 26, 2016 Published: February 25, 2016 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.