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

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

Nature communications (2017-03-02)
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, Karl S Lang
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

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Polyinosinic–polycytidylic acid potassium salt, with buffer salts, TLR ligand tested