An oncolytic adenovirus expressing soluble transforming growth factor-beta type II receptor for targeting breast cancer: in vitro evaluation

Molecular Cancer Therapeutics
Zhen-Guo WangP Seth

Abstract

In recent years, adenoviruses that selectively replicate in tumor cells have been developed. However, there is a tremendous need to improve their anticancer efficacy. We wish to investigate whether a strategy that combines the oncolytic effects of an adenoviral vector with simultaneous expression of soluble form of transforming growth factor-beta type II receptor (sTGFbetaRII) offers a therapeutic advantage. We chose to target TGF-betas because they play a pivotal role in late-stage tumorigenesis by enhancing tumor invasion and metastasis. A sTGFbetaRII cDNA was cloned in conditionally replicating adenoviral vector rAd-sTRII and in a replication-deficient adenovirus Ad-sTRII. Infection of MDA-MB-231 breast cancer cells with rAd-sTRII or Ad-sTRII followed by Western blot analysis indicated the expression of diffused glycosylated forms of sTGFbetaRII that were also secreted into the extracellular medium. The secreted proteins were shown to bind with TGF-beta and antagonize TGF-beta-induced p38 mitogen-activated protein kinase activity. However, marked differences in the replication potential of rAd-sTRII and Ad-sTRII were observed in breast tumor cells. Infection of MDA-MB-231 cells with rAd-sTRII resulted in cytotoxicity and sig...Continue Reading

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Citations

Oct 9, 2008·Breast Cancer Research and Treatment·Antoinette R TanMichael Reiss
Feb 7, 2009·Cancer Gene Therapy·J J Cody, J T Douglas
Dec 13, 2006·Future Oncology·Amy J GalliherWilliam P Schiemann
Aug 6, 2010·Expert Opinion on Biological Therapy·Dong-Sheng PeiJun-Nian Zheng
Oct 11, 2008·Cancer Gene Therapy·B A Guinn, R Mulherkar
May 10, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claudia PenafuerteJacques Galipeau

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