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The resulting severe off\u2010target toxicity of these regimens renders local production at the tumor an attractive concept with possible safety gains. We evaluated the efficacy and safety of intratumorally administered IL\u20102\u2010coding adenoviruses in combination with tumor\u2010infiltrating lymphocyte therapy in syngeneic Syrian hamsters bearing HapT1 pancreatic tumors and with T cell receptor transgenic ACT in B16.OVA melanoma bearing C57BL\/6 mice. The models are complementary: hamsters are semi\u2010permissive for human oncolytic adenovirus, whereas detailed immunological analyses are possible in mice. In both models, local production of IL\u20102 successfully replaced the need for systemic recombinant IL\u20102 (rIL\u20102) administration and increased the efficacy of the cell therapy. Furthermore, vectored delivery of IL\u20102 significantly enhanced the infiltration of CD8+ T cells, M1\u2010like macrophages, and B\u2010cells while systemic rIL\u20102 increased CD25\u2009+\u2009FoxP3+ T cells at the tumor. In contrast with vectored delivery, histopathological analysis of systemic rIL\u20102\u2010treated animals revealed significant changes in lungs, livers, hearts, spleens, and kidneys. In summary, local IL\u20102 production results in efficacy and safety gains in the context of ACT. These preclinical assessments provide the rationale for ongoing clinical translation.<\/jats:p>","DOI":"10.1002\/ijc.30839","type":"journal-article","created":{"date-parts":[[2017,6,14]],"date-time":"2017-06-14T22:34:44Z","timestamp":1497479684000},"page":"1458-1468","source":"Crossref","is-referenced-by-count":22,"title":["Adenoviral production of interleukin\u20102 at the tumor site removes the need for systemic postconditioning in adoptive cell therapy"],"prefix":"10.1002","volume":"141","author":[{"given":"Joao Manuel","family":"Santos","sequence":"first","affiliation":[{"name":"TILT Biotherapeutics Ltd Helsinki Finland"},{"name":"Department of Pathology Faculty of Medicine, Cancer Gene Therapy Group, University of Helsinki  Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riikka","family":"Havunen","sequence":"additional","affiliation":[{"name":"TILT Biotherapeutics Ltd Helsinki Finland"},{"name":"Department of Pathology Faculty of Medicine, Cancer Gene 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