An Oncolytic Adenovirus Encoding Decorin and Granulocyte Macrophage Colony Stimulating Factor Inhibits Tumor Growth in a Colorectal Tumor Model by Targeting Pro-Tumorigenic Signals and via Immune Activation

Human Gene Therapy
Zhao LiuLisheng Wang

Abstract

In advanced and metastatic stages of colorectal cancer (CRC), reduced sensitivity to conventional strategies is still a major obstacle to successful treatments. Decorin is an important regulator in the development and progression of various cancers. To examine if CRC patients have altered decorin levels, expression of decorin and its target genes, Met and vascular endothelial growth factor A (VEGFA), were analyzed in their tumors. Compared to normal tissues, decorin expression was reduced in CRC patients' tumors, while there were increased Met and VEGFA levels. To develop a novel therapy for CRC, rAd.DCN.GM, an oncolytic adenovirus encoding decorin and granulocyte macrophage colony stimulating factor (GM-CSF), has been created. Several therapeutic strategies expressing GM-CSF have been employed in clinical trials for treating metastatic colorectal cancer. In this study, infection of CRC cells with rAd.DCN.GM expressed decorin and GM-CSF, and produced cytotoxicity. In murine CT26 xenografts, rAd.DCN.GM and control adenoviruses were administrated intratumorally on days 7 and 10, and tumor volumes were monitored over time. The study showed that rAd.DCN.GM inhibited the tumor growth and lung metastases significantly. rAd.DCN.GM ind...Continue Reading

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Citations

Mar 1, 2018·British Journal of Pharmacology·Annele Orvokki Sainio, Hannu Tapio Järveläinen
Apr 25, 2020·Current Gene Therapy·Zhong Mian-LingZou Chao-Chun
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Mar 14, 2021·Molecular Diagnosis & Therapy·Sadia Islam Kana, Karim Essani

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
xenograft
FCS
enzyme-linked immunosorbent assay
ELISA
density gradient centrifugation
flow cytometry

Software Mentioned

GraphPad
GraphPad Prism

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