Please use this identifier to cite or link to this item: http://dx.doi.org/10.14279/depositonce-12483
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Main Title: Application Route and Immune Status of the Host Determine Safety and Oncolytic Activity of Oncolytic Coxsackievirus B3 Variant PD-H
Author(s): Hazini, Ahmet
Dieringer, Babette
Klingel, Karin
Pryshliak, Markian
Geisler, Anja
Kobelt, Dennis
Daberkow, Ole
Kurreck, Jens
Linthout, Sophie van
Fechner, Henry
Type: Article
Language Code: en
Abstract: 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.
URI: https://depositonce.tu-berlin.de/handle/11303/13707
http://dx.doi.org/10.14279/depositonce-12483
Issue Date: 24-Sep-2021
Date Available: 11-Oct-2021
DDC Class: 610 Medizin und Gesundheit
Subject(s): coxsackievirus B3
oncolytic virus
cancer
colorectal carcinoma
microRNAs
PD
License: https://creativecommons.org/licenses/by/4.0/
Journal Title: Viruses
Publisher: MDPI
Publisher Place: Basel
Volume: 13
Issue: 10
Article Number: 1918
Publisher DOI: 10.3390/v13101918
EISSN: 1999-4915
Appears in Collections:FG Angewandte Biochemie » Publications

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