Complete regression of human malignant mesothelioma xenografts following local injection of midkine promoter-driven oncolytic adenovirus.

The Journal of Gene Medicine
S KuboHaruki Okamura

Abstract

Malignant mesothelioma is a highly aggressive tumor with poor prognosis. We hypothesized that the tumor-specific midkine (Mdk) promoter could confer transcriptional targeting to oncolytic adenoviruses for effective treatment of malignant mesothelioma. We analysed Mdk expression by quantitative reverse transcription-polymerase chain reaction in six human mesothelioma cell lines, and tested Mdk promoter activity by luciferase reporter assay. On the basis of these data, we constructed a replication-selective oncolytic adenovirus designated AdMdk-E1-iresTK. This virus contains a Mdk promoter-driven adenoviral E1 gene and herpes simplex virus-thymidine kinase (TK) suicide gene and cytomagalovirus promoter-driven enhanced green fluorescent protein marker gene. Selectivity of viral replication and cytolysis were characterized in normal versus mesothelioma cells in vitro, and intratumoral spread and antitumor efficacy were investigated in vivo. Mdk promoter activity was restricted in normal cells, but highly activated in mesothelioma cell lines. AdMdk-E1-iresTK was seen to efficiently replicate, produce viral progeny and spread in multiple mesothelioma cell lines. Lytic spread of AdMdk-E1-iresTK mediated the efficient killing of these ...Continue Reading

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Citations

Mar 14, 2013·BioMed Research International·Yuji TadaMasatoshi Tagawa
Jul 13, 2017·International Journal of Molecular Sciences·Hiroshi TazawaToshiyoshi Fujiwara
Sep 9, 2017·Frontiers in Oncology·Daniel F Pease, Robert A Kratzke
May 26, 2017·Biomedicines·Alexander S Dash, Manish R Patel
Sep 25, 2017·Endocrinology·Chandra C ShenoyGaurang S Daftary

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