1. Synergistic cancer immunotherapy combines MVA-CD40L induced innate and adaptive immunity with tumor targeting antibodies
- Author
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Fabienne Gräbnitz, Ronny Kassub, Barbara Bathke, Sonia T. Wennier, Paul Chaplin, Jose Medina-Echeverz, Marco Testori, Raphael Giessel, Marlene Geiger, Hubertus Hochrein, Henning Lauterbach, Mark Suter, Maria Hinterberger, and Giovanna Fiore
- Subjects
0301 basic medicine ,Antibodies, Neoplasm ,medicine.medical_treatment ,Fc receptor ,General Physics and Astronomy ,Cancer immunotherapy ,Adaptive Immunity ,CD8-Positive T-Lymphocytes ,0302 clinical medicine ,Neoplasms ,Medicine ,lcsh:Science ,Mice, Inbred BALB C ,Vaccines, Synthetic ,Multidisciplinary ,biology ,Vaccination ,Drug Synergism ,Acquired immune system ,Killer Cells, Natural ,030220 oncology & carcinogenesis ,Tumour immunology ,Female ,Immunotherapy ,Cell activation ,Science ,CD40 Ligand ,Antineoplastic Agents ,chemical and pharmacologic phenomena ,Cancer Vaccines ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Immune system ,Adjuvants, Immunologic ,Antigen ,Immunity ,Cell Line, Tumor ,Animals ,Humans ,business.industry ,Viral Vaccines ,General Chemistry ,biochemical phenomena, metabolism, and nutrition ,Immunity, Innate ,Mice, Inbred C57BL ,030104 developmental biology ,Immunization ,Tumour vaccines ,biology.protein ,Cancer research ,lcsh:Q ,business - Abstract
Virus-based vaccines and appropriate costimulation potently enhance antigen-specific T cell immunity against cancer. Here we report the use of recombinant modified vaccinia virus Ankara (rMVA) encoding costimulatory CD40L against solid tumors. Therapeutic treatment with rMVA-CD40L-expressing tumor-associated antigens results in the control of established tumors. The expansion of tumor-specific cytotoxic CD8+ T cells is essential for the therapeutic antitumor effects. Strikingly, rMVA-CD40L also induces strong natural killer (NK) cell activation and expansion. Moreover, the combination of rMVA-CD40L and tumor-targeting antibodies results in increased therapeutic antitumor efficacy relying on the presence of Fc receptor and NK cells. We describe a translationally relevant therapeutic synergy between systemic viral vaccination and CD40L costimulation. We show strengthened antitumor immune responses when both rMVA-CD40L-induced innate and adaptive immune mechanisms are exploited by combination with tumor-targeting antibodies. This immunotherapeutic approach could translate into clinical cancer therapies where tumor-targeting antibodies are employed., CD40 agonists have been investigated as a strategy to awaken the immune system against cancers. Here, the authors use a virus encoding CD40L and tumour-associated antigens to enhance innate and adaptive immunity that together with tumour targeting antibodies controls the growth of tumours in mice.
- Published
- 2019
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