Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression

Halime Kalkavan, Piyush Sharma, Stefan Kasper, Iris Helfrich, Aleksandra A. Pandyra, Asmae Gassa, Isabel Virchow, Lukas Flatz, Tim Brandenburg, Sukumar Namineni, Mathias Heikenwalder, Bastian Höchst, Percy A. Knolle, Guido Wollmann, Dorothee von Laer, Ingo Drexler, Jessica Rathbun, Paula M. Cannon, Stefanie Scheu, Jens Bauer, Jagat Chauhan, Dieter Häussinger, Gerald Willimsky, Max Löhning, Dirk Schadendorf, Sven Brandau, Martin Schuler (), Philipp A. Lang and Karl S. Lang ()
Additional contact information
Halime Kalkavan: Institute of Immunology, Medical Faculty, University Duisburg-Essen
Piyush Sharma: Institute of Immunology, Medical Faculty, University Duisburg-Essen
Stefan Kasper: West German Cancer Center, University Hospital Essen, University Duisburg-Essen
Iris Helfrich: West German Cancer Center, University Hospital Essen, University Duisburg-Essen
Aleksandra A. Pandyra: Institute of Immunology, Medical Faculty, University Duisburg-Essen
Asmae Gassa: Institute of Immunology, Medical Faculty, University Duisburg-Essen
Isabel Virchow: West German Cancer Center, University Hospital Essen, University Duisburg-Essen
Lukas Flatz: Cantonal Hospital
Tim Brandenburg: Institute of Immunology, Medical Faculty, University Duisburg-Essen
Sukumar Namineni: Technical University of Munich
Mathias Heikenwalder: Technical University of Munich
Bastian Höchst: Institute of Molecular Immunology/Experimental Oncology, München Klinikum rechts der Isar, Technical University Munich
Percy A. Knolle: Institute of Molecular Immunology/Experimental Oncology, München Klinikum rechts der Isar, Technical University Munich
Guido Wollmann: Medical University Innsbruck
Dorothee von Laer: Medical University Innsbruck
Ingo Drexler: Institute of Virology, Düsseldorf University Hospital, Heinrich Heine University
Jessica Rathbun: University of Southern California
Paula M. Cannon: University of Southern California
Stefanie Scheu: Institute of Medical Microbiology and Hospital Hygiene, University of Düsseldorf
Jens Bauer: Institute of Medical Microbiology and Hospital Hygiene, University of Düsseldorf
Jagat Chauhan: Ludwig Institute for Cancer Research, University of Oxford
Dieter Häussinger: Hepatology and Infectious Diseases, University of Düsseldorf
Gerald Willimsky: Institute of Immunology (Charité - University Medicine Berlin)
Max Löhning: Charité—University Medicine Berlin and German Rheumatism Research Center (DRFZ)
Dirk Schadendorf: West German Cancer Center, University Hospital Essen, University Duisburg-Essen
Sven Brandau: West German Cancer Center, University Hospital Essen, University Duisburg-Essen
Martin Schuler: West German Cancer Center, University Hospital Essen, University Duisburg-Essen
Philipp A. Lang: Medical Faculty, Heinrich Heine University
Karl S. Lang: Institute of Immunology, Medical Faculty, University Duisburg-Essen

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract Immune-mediated effector molecules can limit cancer growth, but lack of sustained immune activation in the tumour microenvironment restricts antitumour immunity. New therapeutic approaches that induce a strong and prolonged immune activation would represent a major immunotherapeutic advance. Here we show that the arenaviruses lymphocytic choriomeningitis virus (LCMV) and the clinically used Junin virus vaccine (Candid#1) preferentially replicate in tumour cells in a variety of murine and human cancer models. Viral replication leads to prolonged local immune activation, rapid regression of localized and metastatic cancers, and long-term disease control. Mechanistically, LCMV induces antitumour immunity, which depends on the recruitment of interferon-producing Ly6C+ monocytes and additionally enhances tumour-specific CD8+ T cells. In comparison with other clinically evaluated oncolytic viruses and to PD-1 blockade, LCMV treatment shows promising antitumoural benefits. In conclusion, therapeutically administered arenavirus replicates in cancer cells and induces tumour regression by enhancing local immune responses.

Date: 2017
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DOI: 10.1038/ncomms14447

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