{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:07:59Z","timestamp":1785236879129,"version":"3.55.0"},"reference-count":54,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","award":["2017.101.1"],"award-info":[{"award-number":["2017.101.1"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","award":["2021.049.1"],"award-info":[{"award-number":["2021.049.1"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006764","name":"Technische Universit\u00e4t Berlin","doi-asserted-by":"publisher","award":["17011\/1TUB"],"award-info":[{"award-number":["17011\/1TUB"]}],"id":[{"id":"10.13039\/501100006764","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Excellence strategy of the Federation and Federal States by the Berlin University Alliance","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The coxsackievirus B3 strain PD-0 has been proposed as a new oncolytic virus for the treatment of colorectal carcinoma. Here, we generated a cDNA clone of PD-0 and analyzed the virus PD-H, newly generated from this cDNA, in xenografted and syngenic models of colorectal cancer. Replication and cytotoxic assays revealed that PD-H replicated and lysed colorectal carcinoma cell lines in vitro as well as PD-0. Intratumoral injection of PD-H into subcutaneous DLD-1 tumors in nude mice resulted in strong inhibition of tumor growth and significantly prolonged the survival of the animals, but virus-induced systemic infection was observed in one of the six animals. In a syngenic mouse model of subcutaneously growing Colon-26 tumors, intratumoral administration of PD-H led to a significant reduction of tumor growth, the prolongation of animal survival, the prevention of tumor-induced cachexia, and the elevation of CD3+ and dendritic cells in the tumor microenvironment. No virus-induced side effects were observed. After intraperitoneal application, PD-H induced weak pancreatitis and myocarditis in immunocompetent mice. By equipping the virus with target sites of miR-375, which is specifically expressed in the pancreas, organ infections were prevented. Moreover, employment of this virus in a syngenic mouse model of CT-26 peritoneal carcinomatosis resulted in a significant reduction in tumor growth and an increase in animal survival. The results demonstrate that the immune status of the host, the route of virus application, and the engineering of the virus with target sites of suitable microRNAs are crucial for the use of PD-H as an oncolytic virus.<\/jats:p>","DOI":"10.3390\/v13101918","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T23:08:31Z","timestamp":1632784111000},"page":"1918","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Application Route and Immune Status of the Host Determine Safety and Oncolytic Activity of Oncolytic Coxsackievirus B3 Variant PD-H"],"prefix":"10.3390","volume":"13","author":[{"given":"Ahmet","family":"Hazini","sequence":"first","affiliation":[{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, 13355 Berlin, Germany"},{"name":"Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babette","family":"Dieringer","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, 13355 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0203-2498","authenticated-orcid":false,"given":"Karin","family":"Klingel","sequence":"additional","affiliation":[{"name":"Cardiopathology, Institute for Pathology and Neuropathology, University Hospital Tuebingen, 72076 Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0001-8270","authenticated-orcid":false,"given":"Markian","family":"Pryshliak","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, 13355 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Geisler","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, 13355 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9373-0648","authenticated-orcid":false,"given":"Dennis","family":"Kobelt","sequence":"additional","affiliation":[{"name":"EPO GmbH Berlin-Buch, Robert-R\u00f6ssle Str. 10, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Daberkow","sequence":"additional","affiliation":[{"name":"EPO GmbH Berlin-Buch, Robert-R\u00f6ssle Str. 10, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1469-0052","authenticated-orcid":false,"given":"Jens","family":"Kurreck","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, 13355 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie van","family":"Linthout","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health Center for Regenerative Therapies (BCRT), Campus Virchow Klinikum (CVK), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, F\u00f6hrer Str. 15, 13353 Berlin, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Berlin\u2014Charit\u00e9, Oudenarder Stra\u00dfe 16, 13316 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7082-4350","authenticated-orcid":false,"given":"Henry","family":"Fechner","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, 13355 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/sj.mt.6300108","article-title":"History of Oncolytic Viruses: Genesis to Genetic Engineering","volume":"15","author":"Kelly","year":"2007","journal-title":"Mol. 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