title: 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.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia.
authors.forename: Belal M
authors.initials: BM
authors.lastname: Azab
authors.forename: Rupesh
authors.initials: R
authors.lastname: Dash
authors.forename: Swadesh K
authors.initials: SK
authors.lastname: Das
authors.forename: Sujit K
authors.initials: SK
authors.lastname: Bhutia
authors.forename: Siddik
authors.initials: S
authors.lastname: Sarkar
authors.forename: Xue-Ning
authors.initials: XN
authors.lastname: Shen
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Quinn
authors.forename: Paul
authors.initials: P
authors.lastname: Dent
authors.forename: Igor P
authors.initials: IP
authors.lastname: Dmitriev
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Wang
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellecchia
authors.forename: John C
authors.initials: JC
authors.lastname: Reed
authors.forename: Devanand
authors.initials: D
authors.lastname: Sarkar
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000235:genetics* / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012703:Serotyping; D023041:Xenograft Model Antitumor Assays
chemical_list: D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011994:Recombinant Proteins