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

Publication

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

Journal Paper/Review - Mar 1, 2017

Kalkavan Halime, Rathbun Jessica, Cannon Paula M, Scheu Stefanie, Bauer Jens, Chauhan Jagat, Häussinger Dieter, Willimsky Gerald, Löhning Max, Schadendorf Dirk, Brandau Sven, Schuler Martin, Lang Philipp A, Drexler Ingo, von Laer Dorothee, Wollmann Guido, Sharma Piyush, Kasper Stefan, Helfrich Iris, Pandyra Aleksandra A, Gassa Asmae, Virchow Isabel, Flatz Lukas, Brandenburg Tim, Namineni Sukumar, Heikenwalder Mathias, Höchst Bastian, Knolle Percy A, Lang Karl S

Citation

Kalkavan H, Rathbun J, Cannon P, Scheu S, Bauer J, Chauhan J, Häussinger D, Willimsky G, Löhning M, Schadendorf D, Brandau S, Schuler M, Lang P, Drexler I, von Laer D, Wollmann G, Sharma P, Kasper S, Helfrich I, Pandyra A, Gassa A, Virchow I, Flatz L, Brandenburg T, Namineni S, Heikenwalder M, Höchst B, Knolle P, Lang K. Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression. Nat Commun 2017; 8:14447.

Type

Journal Paper/Review (English)

Journal

Nat Commun 2017; 8

Publication Date

Mar 1, 2017

Issn Electronic

2041-1723

Pages

14447

Brief description/objective

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.