Wennhold et al. isolated murine antigen-specific B cells, enhanced their antigen presentation capabilities with CD40 stimulation, and showed T cell stimulating properties in vitro and in vivo equivalent to dendritic cells (DC). Combining these DC-like B cells with antigen-specific B cells expressing antibody (following stimulation with CD40, IL-21, and IL-4) significantly enhanced therapeutic efficacy in a pancreatic tumor model. Similar DC-like B cells were isolated from draining lymph nodes or TILs in human cancers.
Cancer immunotherapy by therapeutic activation of T cells has demonstrated clinical potential. Approaches include checkpoint inhibitors and chimeric antigen receptor T cells. Here, we report the development of an alternative strategy for cellular immunotherapy that combines induction of a tumor-directed T-cell response and antibody secretion without the need for genetic engineering. CD40 ligand stimulation of murine tumor antigen-specific B cells, isolated by antigen-biotin tetramers, resulted in the development of an antigen-presenting phenotype and the induction of a tumor antigen-specific T-cell response. Differentiation of antigen-specific B cells into antibody-secreting plasma cells was achieved by stimulation with interleukin 21 (IL-21), interleukin 4 (IL-4), anti-CD40, and the specific antigen. Combined treatment of tumor-bearing mice with antigen-specific CD40-activated B cells and antigen-specific plasma cells induced a therapeutic antitumor immune response resulting in remission of established tumors. Human CEA or NY-ESO-1-specific B cells were detected in tumor-draining lymph nodes and were able to induce antigen-specific T-cell responses in vitro indicating that this approach could be translated into clinical applications. Our results describe a technique for the exploitation of B cell-effector functions and provide the rationale for their use in combinatorial cancer immunotherapy.
Author Info: (1) Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne kerstin.wennhold@uk-koeln.de. (2) Cologne Interventional Immunology (
Author Info: (1) Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne kerstin.wennhold@uk-koeln.de. (2) Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne. (3) Department of General, Visceral and Cancer Surgery, University Hospital of Cologne. (4) Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne. (5) Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne. (6) Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne. (7) Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Cologne. (8) Center of Integrated Protein Science Munich (CIPSM) and Division of Clinical Pharmacology, University Hospital Munich, Medical Clinic and Policlinic IV. (9) Center of Integrated Protein Science Munich (CIPSM) and Division of Clinical Pharmacology, University Hospital Munich, Medical Clinic and Policlinic IV. (10) Department for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne. (11) Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne. (12) Laboratory for Cancer-Immuno-Metabolism, Department I of Internal Medicine, University Hospital of Cologne. (13) Department I for Internal Medicine, University Hospital of Cologne. (14) Center for Molecular Medicine Cologne, University of Cologne. (15) Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne. (16) Cologne Interventional Immunology (CII), Department I of Internal Medicine, University Hospital of Cologne.
