Using antigen-specific B cells to combine antibody and T-cell based cancer immunotherapy.

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Using antigen-specific B cells to combine antibody and T-cell based cancer immunotherapy.

Cancer Immunol Res. 2017 Aug 04;:

Authors: Wennhold K, Thelen M, Schloesser HA, Haustein N, Reuter S, Garcia-Marquez M, Lechner A, Kobold S, Rataj F, Utermoehlen O, Chakupurakal G, Theurich S, Hallek M, Abken H, Shimabukuro-Vornhagen A, von Bergwelt-Baildon M

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 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.

PMID: 28778961 [PubMed - as supplied by publisher]

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