Comparison of molecular strategies for breast cancer virotherapy using oncolytic adenovirus

Human Gene Therapy
Miriam Bazan-PeregrinoLeonard W Seymour

Abstract

Oncolytic viruses are regulated by the tumor phenotype to replicate and lyse cancer cells selectively. To identify optimal strategies for breast cancer we compared five adenoviruses with distinct regulatory mechanisms: Ad-dl922-947 (targets G1-S checkpoint); Ad-Onyx-015 and Ad-Onyx-017 (target p53/mRNA export); Ad-vKH1 (targets Wnt pathway), and AdEHE2F (targets estrogen receptor/G1-S checkpoint/hypoxic signaling). The quantity of virus required to kill 50% of breast cancer cells after 6 days (EC(50), plaque-forming units per cell) was measured. The most potent virus was Ad-dl922-947 (EC(50), 0.01-5.4 in SkBr3, MDA-231, MDA-468, MCF7, and ZR75.1 cells), followed by wild-type (Ad-WT; EC(50), 0.3-5.5) and AdEHE2F (EC(50), 1.4-3.9). Ad-vKH1 (EC(50), 7.2-72.1), Ad-Onyx-017 (EC(50), 8.4-167), and Ad-Onyx-015 (EC(50), 17.7-377) showed less activity. Most viruses showed limited cytotoxicity in normal human cells, including breast epithelium MCF10A (EC(50), >722) and fibroblasts (EC(50), >192) and only moderate cytotoxicity in normal microvascular endothelial cells (HMVECs; EC(50), 42.8-149), except Ad-dl922-947, which was active in HMVECs (EC(50), 1.6). After injection into MDA-231 xenografts, Ad-WT, AdEHE2F, and Ad-dl922-947 showed r...Continue Reading

References

Jul 1, 1978·The Journal of General Virology·S J DuncanH N Willcox
Jan 1, 1989·Cancer Chemotherapy and Pharmacology·M M Tomayko, C P Reynolds
Dec 1, 1989·Virus Research·G E BlairM E Zajdel
Oct 21, 1999·Analytical Biochemistry·P Murakami, M T McCaman
Aug 22, 2002·Cancer Gene Therapy·Jaesung KimChae-Ok Yun
Oct 25, 2002·Human Gene Therapy·Ruben Hernandez-AlcocebaMichael F Clarke
May 13, 2003·Reviews in Medical Virology·Tsoline KojaoghlanianMarshall S Horwitz
Jan 24, 2004·Cancer Biology & Therapy·Louise R Howe, Anthony M C Brown
Sep 24, 2004·Current Gene Therapy·Maaike Everts, David T Curiel
Nov 19, 2005·Nature Reviews. Cancer·Kelley A ParatoJohn C Bell
May 10, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Farin KamangarWilliam F Anderson
Feb 23, 2007·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·Gulisa TurashviliZdenek Kolar
Mar 10, 2007·Current Cancer Drug Targets·Anne Moon Crompton, David H Kirn
Aug 31, 2007·Expert Opinion on Biological Therapy·Marianne M Stanford, Grant McFadden
Oct 25, 2007·Cellular and Molecular Life Sciences : CMLS·K LundgrenG Landberg
Feb 29, 2008·Journal of Virology·L A SeifriedF A Dick

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Citations

Jul 13, 2013·Cancer Gene Therapy·M Bazan-PeregrinoL W Seymour
Oct 31, 2013·Journal of the National Cancer Institute·Robert CarlisleLeonard W Seymour
May 14, 2010·Cold Spring Harbor Perspectives in Biology·David P LaneSonia Lain
Jan 14, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniel ObergGunnel Halldén
Feb 27, 2014·Human Gene Therapy Methods·Gray KueberuwaLeonard W Seymour
Apr 9, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Miriam Bazan-PeregrinoConstantin C Coussios
Apr 28, 2009·Advanced Drug Delivery Reviews·Dominik E Dorer, Dirk M Nettelbeck
Aug 21, 2009·Veterinary and Comparative Oncology·M ArendtI M Morgan
Jul 2, 2011·British Journal of Pharmacology·Frank Essmann, Klaus Schulze-Osthoff
Jan 11, 2014·Journal of Hepato-biliary-pancreatic Sciences·Kulthida VaeteewoottacharnSopit Wongkham
Oct 11, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Miriam Bazan-PeregrinoConstantin-C Coussios
Apr 2, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eduardo G CafferataOsvaldo L Podhajcer

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