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Nat Commun. 2017 Mar 1;8:14447. doi: 10.1038/ncomms14447.

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

Author information

1
Institute of Immunology, Medical Faculty, University Duisburg-Essen, 45122 Essen, Germany.
2
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
3
Department of Dermatology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
4
Department of Cardiothoracic Surgery, Cologne University Heart Center, Kerpener Strasse 62, 50937 Cologne, Germany.
5
Department of Dermatology/Allergology, Cantonal Hospital, Rorschacher Strasse 95, St. Gallen 9007, Switzerland.
6
Department of Virology, Technical University of Munich, Schneckenburgstrasse 8, 81675 Munich, Germany.
7
Institute of Molecular Immunology/Experimental Oncology, München Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany.
8
Division for Virology, Medical University Innsbruck, Peter-Mayr-Strasse 4b, 6020 Innsbruck, Austria.
9
Institute of Virology, Düsseldorf University Hospital, Heinrich Heine University, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
10
Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, 90033 California, USA.
11
Institute of Medical Microbiology and Hospital Hygiene, University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
12
Ludwig Institute for Cancer Research, University of Oxford, Old Road Campus, Research Building, Old Road Campus, Headington, Oxford OX3 7DQ, UK.
13
Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
14
Institute of Immunology (Charité - University Medicine Berlin), 3125 Berlin, Germany.
15
German Cancer Research Center (DKFZ), 13125 Heidelberg, Germany.
16
Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin and German Rheumatism Research Center (DRFZ), Charitéplatz 1, D-10117 Berlin, Germany.
17
German Cancer Consortium (DKTK), Partner Site University Hospital Essen, 45122 Essen, Germany.
18
Department of Otorhinolaryngology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
19
Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.

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.

PMID:
28248314
PMCID:
PMC5337983
DOI:
10.1038/ncomms14447
[Indexed for MEDLINE]
Free PMC Article

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