Enhanced prostate cancer gene transfer and therapy using a novel serotype chimera cancer terminator virus (Ad.5/3-CTV).

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.

• Authors: 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
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 229 Issue 1 Pg. 34-43 (Jan 2014) ISSN: 1097-4652 [Electronic] United States
• PMID: 23868767 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Wiley Periodicals, Inc.

Chemical References

• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Recombinant Proteins

Topics

• Adenoviridae (genetics)
• Animals
• Cell Line, Tumor
• Cell Survival (genetics)
• Coxsackie and Adenovirus Receptor-Like Membrane Protein (genetics, therapeutic use)
• Gene Transfer Techniques
• Genetic Therapy
• Humans
• Male
• Mice
• Mice, Nude
• Oncolytic Virotherapy
• Oncolytic Viruses (genetics)
• Prostatic Neoplasms (genetics, pathology, therapy)
• Recombinant Proteins (therapeutic use)
• Serotyping
• Xenograft Model Antitumor Assays