Enhanced Prostate Cancer Gene Transfer and Therapy Using a Novel Serotype Chimera Cancer Terminator Virus (Ad.5/3-CTV)

Belal M. Azab, Rupesh Dash, Swadesh K. Das, Sujit K. Bhutia, Siddik Sarkar, Xue Ning Shen, Bridget A. Quinn, Paul Dent, Igor P. Dmitriev, Xiang Yang Wang, David T. Curiel, Maurizio Pellecchia, John C. Reed, Devanand Sarkar, Paul B. Fisher

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16 Scopus citations

Abstract

Few options are available for treating patients with advanced prostate cancer (PC). As PC is a slow growing disease and accessible by ultrasound, gene therapy could provide a viable option for this neoplasm. Conditionally replication-competent adenoviruses (CRCAs) represent potentially useful reagents for treating PC. We previously constructed a CRCA, cancer terminator virus (CTV), which showed efficacy both in vitro and in vivo for PC. The CTV was generated on a serotype 5-background (Ad.5-CTV) with infectivity depending on Coxsackie-Adenovirus Receptors (CARs). CARs are frequently reduced in many tumor types, including PCs thereby limiting effective Ad-mediated therapy. Using serotype chimerism, a novel CTV (Ad.5/3-CTV) was created by replacing the Ad.5 fiber knob with the Ad.3 fiber knob thereby facilitating infection in a CAR-independent manner. We evaluated Ad.5/3-CTV in comparison with Ad.5-CTV in low CAR human PC cells, demonstrating higher efficiency in inhibiting cell viability in vitro. Moreover, Ad.5/3-CTV potently suppressed in vivo tumor growth in a nude mouse xenograft model and in a spontaneously induced PC that develops in Hi-myc transgenic mice. Considering the significant responses in a Phase I clinical trial of a non-replicating Ad.5-mda-7 in advanced cancers, Ad.5/3-CTV may exert improved therapeutic benefit in a clinical setting.

Original languageEnglish
Pages (from-to)34-43
Number of pages10
JournalJournal of Cellular Physiology
Volume229
Issue number1
DOIs
StatePublished - Jan 1 2014

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    Azab, B. M., Dash, R., Das, S. K., Bhutia, S. K., Sarkar, S., Shen, X. N., Quinn, B. A., Dent, P., Dmitriev, I. P., Wang, X. Y., Curiel, D. T., Pellecchia, M., Reed, J. C., Sarkar, D., & Fisher, P. B. (2014). Enhanced Prostate Cancer Gene Transfer and Therapy Using a Novel Serotype Chimera Cancer Terminator Virus (Ad.5/3-CTV). Journal of Cellular Physiology, 229(1), 34-43. https://doi.org/10.1002/jcp.24408