Using Antigen-Specific B Cells to Combine Antibody and T Cell-Based Cancer Immunotherapy

Wennhold, Kerstin; Thelen, Martin; Schlösser, Hans Anton; Haustein, Natalie; Reuter, Sabrina; Garcia-Marquez, Maria; Lechner, Axel; Kobold, Sebastian; Rataj, Felicitas; Utermöhlen, Olaf; Chakupurakal, Geothy; Theurich, Sebastian; Hallek, Michäl; Abken, Hinrich; Shimabukuro-Vornhagen, Alexander; Bergwelt-Baildon, Michäl von (2017): Using Antigen-Specific B Cells to Combine Antibody and T Cell-Based Cancer Immunotherapy. In: Cancer Immunology Research, Vol. 5, No. 9: pp. 730-743

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
• Faculties: Medicine
• Research Centers: Center for Integrated Protein Science Munich (CIPSM)
• Subjects: 600 Technology > 610 Medicine and health; 500 Science > 540 Chemistry
• ISSN: 2326-6066
• Language: English