Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression
Abstract & Authors:展开
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.
Martin Schuler,Karl S Lang
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