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Using a chimeric vesicular stomatitis virus variant VSV-GP, we addressed the direct oncolytic effects and the role of anti-tumour immune induction in the syngeneic mouse lung cancer model LLC1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To study a tumour system with limited antiviral effects, we generated interferon receptor-deficient cells (LLC1-IFNAR1<jats:sup>\u2212\/\u2212<\/jats:sup>). Therapeutic efficacy of VSV-GP was assessed in vivo in syngeneic C57BL\/6 and athymic nude mice bearing subcutaneous tumours. VSV-GP treatment effects were analysed using bioluminescent imaging (BLI), immunohistochemistry, ELISpot, flow cytometry, multiplex ELISA and Nanostring\u00ae assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Interferon insensitivity correlated with VSV-GP replication and therapeutic outcome. BLI revealed tumour-to-tumour spread of viral progeny in bilateral tumours. Histological and gene expression analysis confirmed widespread and rapid infection and cell killing within the tumour with activation of innate and adaptive immune-response markers. However, treatment outcome was increased in the absence of CD8<jats:sup>+<\/jats:sup>T\u00a0cells and surviving mice showed little protection from tumour re-challenge, indicating limited therapeutic contribution by the activated immune system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These studies present a case for a predominantly lytic treatment effect of VSV-GP in a syngeneic mouse lung cancer model.<\/jats:p><\/jats:sec>","DOI":"10.1038\/s41416-019-0574-7","type":"journal-article","created":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T23:03:53Z","timestamp":1568761433000},"page":"647-658","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["The lytic activity of VSV-GP treatment dominates the therapeutic effects in a syngeneic model of lung cancer"],"prefix":"10.1038","volume":"121","author":[{"given":"Liesa-Marie","family":"Schreiber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carles","family":"Urbiola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Spiesschaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Kimpel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Heinemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Stierstorfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Petersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Erlmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"von Laer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Wollmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,18]]},"reference":[{"key":"574_CR1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s40425-016-0158-5","volume":"4","author":"H Rehman","year":"2016","unstructured":"Rehman, H., Silk, A. 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D.v.L. and G.W. serve as scientific advisors for Boehringer Ingelheim GmbH. F.H., B.St. and P.M. are employees of Boehringer Ingelheim Pharma GmbH. B.Sp., M.P. and P.E. are employees of ViraTherapeutics GmbH. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The studies were performed in compliance with the Austrian experimentation law. Animal trial permission was granted by the national authorities (BMWFW-66.011\/0012-WF\/V\/3b\/2016 and BMWFW-66.011\/0041-WF\/V\/3b\/2016).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"This study was supported by a grant from the Christian Doppler Research Association (L.M.S., C.U., B.S., G.W.).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"All pertinent data to support this study are included in the manuscript and supplementary files. Further data supporting the findings are available upon request.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}}]}}