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.
Dokumententyp: | Zeitschriftenartikel |
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Fakultät: | Medizin |
Fakultätsübergreifende Einrichtungen: | Center for Integrated Protein Science Munich (CIPSM) |
Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
500 Naturwissenschaften und Mathematik > 540 Chemie |
ISSN: | 2326-6066 |
Sprache: | Englisch |
Dokumenten ID: | 50002 |
Datum der Veröffentlichung auf Open Access LMU: | 14. Jun. 2018, 09:42 |
Letzte Änderungen: | 23. Dez. 2020, 13:22 |