Wennhold, Kerstin ORCID: 0000-0001-5539-7226, Thelen, Martin ORCID: 0000-0002-2785-9726, Schloesser, Hans Anton, Haustein, Natalie, Reuter, Sabrina, Garcia-Marquez, Maria, Lechner, Axel, Kobold, Sebastian, Rataj, Felicitas, Utermoehlen, Olaf, Chakupurakal, Geothy, Theurich, Sebastian ORCID: 0000-0001-5706-8258, Hallek, Michael, Abken, Hinrich, Shimabukuro-Vornhagen, Alexander and von Bergwelt-Baildon, Michael (2017). Using Antigen-Specific B Cells to Combine Antibody and T Cell-Based Cancer Immunotherapy. Cancer Immunol. Res., 5 (9). S. 730 - 744. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 2326-6074

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Abstract

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 tumordirected T-cell response and antibody secretion without the need for genetic engineering. CD40 ligand stimulation of murine tumor antigen-specific B cells, isolated by antigenbiotin tetramers, resulted in the development of an antigenpresenting phenotype and the induction of a tumor antigenspecific T-cell response. Differentiation of antigen-specific B cells into antibody-secreting plasma cells was achieved by stimulation with IL21, IL4, anti-CD40, and the specific antigen. Combined treatment of tumor-bearing mice with antigenspecific CD40-activated B cells and antigen-specific plasma cells induced a therapeutic antitumor immune response resulting in remission of established tumors. Human CEA or NYESO- 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. (C) 2017 AACR.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wennhold, KerstinUNSPECIFIEDorcid.org/0000-0001-5539-7226UNSPECIFIED
Thelen, MartinUNSPECIFIEDorcid.org/0000-0002-2785-9726UNSPECIFIED
Schloesser, Hans AntonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haustein, NatalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reuter, SabrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Marquez, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lechner, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kobold, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rataj, FelicitasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Utermoehlen, OlafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chakupurakal, GeothyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Theurich, SebastianUNSPECIFIEDorcid.org/0000-0001-5706-8258UNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abken, HinrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shimabukuro-Vornhagen, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Bergwelt-Baildon, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-220624
DOI: 10.1158/2326-6066.CIR-16-0236
Journal or Publication Title: Cancer Immunol. Res.
Volume: 5
Number: 9
Page Range: S. 730 - 744
Date: 2017
Publisher: AMER ASSOC CANCER RESEARCH
Place of Publication: PHILADELPHIA
ISSN: 2326-6074
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PRESENTING CELLS; REGULATORY CELLS; DENDRITIC CELLS; RESPONSES; ACTIVATION; EXPRESSION; IMMUNITY; FORMMultiple languages
Oncology; ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22062

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