Application Route and Immune Status of the Host Determine Safety and Oncolytic Activity of Oncolytic Coxsackievirus B3 Variant PD-H

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dc.contributor.authorHazini, Ahmet
dc.contributor.authorDieringer, Babette
dc.contributor.authorKlingel, Karin
dc.contributor.authorPryshliak, Markian
dc.contributor.authorGeisler, Anja
dc.contributor.authorKobelt, Dennis
dc.contributor.authorDaberkow, Ole
dc.contributor.authorKurreck, Jens
dc.contributor.authorLinthout, Sophie van
dc.contributor.authorFechner, Henry
dc.date.accessioned2021-10-11T12:49:55Z
dc.date.available2021-10-11T12:49:55Z
dc.date.issued2021-09-24
dc.date.updated2021-10-01T18:51:52Z
dc.description.abstractThe 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.en
dc.description.sponsorshipDFG, 414044773, Open Access Publizieren 2021 - 2022 / Technische Universität Berlinen
dc.identifier.eissn1999-4915
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/13707
dc.identifier.urihttp://dx.doi.org/10.14279/depositonce-12483
dc.language.isoenen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subject.ddc610 Medizin und Gesundheitde
dc.subject.othercoxsackievirus B3en
dc.subject.otheroncolytic virusen
dc.subject.othercanceren
dc.subject.othercolorectal carcinomaen
dc.subject.othermicroRNAsen
dc.subject.otherPDen
dc.titleApplication Route and Immune Status of the Host Determine Safety and Oncolytic Activity of Oncolytic Coxsackievirus B3 Variant PD-Hen
dc.typeArticleen
dc.type.versionpublishedVersionen
dcterms.bibliographicCitation.articlenumber1918en
dcterms.bibliographicCitation.doi10.3390/v13101918en
dcterms.bibliographicCitation.issue10en
dcterms.bibliographicCitation.journaltitleVirusesen
dcterms.bibliographicCitation.originalpublishernameMDPIen
dcterms.bibliographicCitation.originalpublisherplaceBaselen
dcterms.bibliographicCitation.volume13en
tub.accessrights.dnbfreeen
tub.affiliationFak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Angewandte Biochemiede
tub.affiliation.facultyFak. 3 Prozesswissenschaftende
tub.affiliation.groupFG Angewandte Biochemiede
tub.affiliation.instituteInst. Biotechnologiede
tub.publisher.universityorinstitutionTechnische Universität Berlinen

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