Kalkavan, Halime ORCID: 0000-0002-0090-4080, Sharma, Piyush ORCID: 0000-0003-1185-9534, Kasper, Stefan ORCID: 0000-0002-5947-8733, Helfrich, Iris, Pandyra, Aleksandra A., Gassa, Asmae, Virchow, Isabel, Flatz, Lukas, Brandenburg, Tim, Namineni, Sukumar, Heikenwalder, Mathias, Hoechst, Bastian, Knolle, Percy A. ORCID: 0000-0003-2983-0414, Wollmann, Guido, von Laer, Dorothee, Drexler, Ingo, Rathbun, Jessica, Cannon, Paula M., Scheu, Stefanie ORCID: 0000-0002-9707-8191, Bauer, Jens, Chauhan, Jagat, Haeussinger, Dieter, Willimsky, Gerald, Lohning, Max ORCID: 0000-0001-6382-7281, Schadendorf, Dirk, Brandau, Sven ORCID: 0000-0002-2702-4163, Schuler, Martin, Lang, Philipp A. and Lang, Karl S. (2017). Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression. Nat. Commun., 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kalkavan, HalimeUNSPECIFIEDorcid.org/0000-0002-0090-4080UNSPECIFIED
Sharma, PiyushUNSPECIFIEDorcid.org/0000-0003-1185-9534UNSPECIFIED
Kasper, StefanUNSPECIFIEDorcid.org/0000-0002-5947-8733UNSPECIFIED
Helfrich, IrisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pandyra, Aleksandra A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gassa, AsmaeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Virchow, IsabelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Flatz, LukasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brandenburg, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Namineni, SukumarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heikenwalder, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoechst, BastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knolle, Percy A.UNSPECIFIEDorcid.org/0000-0003-2983-0414UNSPECIFIED
Wollmann, GuidoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Laer, DorotheeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drexler, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rathbun, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cannon, Paula M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheu, StefanieUNSPECIFIEDorcid.org/0000-0002-9707-8191UNSPECIFIED
Bauer, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chauhan, JagatUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haeussinger, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Willimsky, GeraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lohning, MaxUNSPECIFIEDorcid.org/0000-0001-6382-7281UNSPECIFIED
Schadendorf, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brandau, SvenUNSPECIFIEDorcid.org/0000-0002-2702-4163UNSPECIFIED
Schuler, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, Philipp A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, Karl S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-238651
DOI: 10.1038/ncomms14447
Journal or Publication Title: Nat. Commun.
Volume: 8
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LYMPHOCYTIC CHORIOMENINGITIS VIRUS; VESICULAR STOMATITIS-VIRUS; DENDRITIC CELLS; CANCER-CELLS; ONCOLYTIC ADENOVIRUS; TOXOPLASMA-GONDII; VIRAL REPLICATION; INFECTION; BETA; MONOCYTESMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23865

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