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Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression #MMPMID28248314
Kalkavan H; Sharma P; Kasper S; Helfrich I; Pandyra AA; Gassa A; Virchow I; Flatz L; Brandenburg T; Namineni S; Heikenwalder M; Höchst B; Knolle PA; Wollmann G; von Laer D; Drexler I; Rathbun J; Cannon PM; Scheu S; Bauer J; Chauhan J; Häussinger D; Willimsky G; Löhning M; Schadendorf D; Brandau S; Schuler M; Lang PA; Lang KS
Nat Commun 2017[]; 8 (ä): ä PMID28248314show ga
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.