Intravesical Ad-IFNalpha causes marked regression of human bladder cancer growing orthotopically in nude mice and overcomes resistance to IFN-alpha protein

Molecular Therapy : the Journal of the American Society of Gene Therapy
William BenedictRobert J Connor

Abstract

We have produced prolonged, high local concentrations of interferon in vivo by intravesical instillation of adenoviruses encoding interferon-alpha (Ad-IFNalpha) together with the gene transfer-enhancing agent Syn3. We found sustained interferon protein levels for days, both in normal mouse urothelium and in human bladder cancer cells growing as superficial bladder tumors in nude mice using an orthotopic bladder model developed by us. Tumor burden in the bladder was determined utilizing cancer cells containing the green fluorescent protein. Marked tumor regression was observed following two 1-h exposures of Ad-IFNalpha/Syn3 and little or no cytotoxicity was detected in normal cells. Similar intravesical instillation of clinically relevant concentrations of IFN protein alone or Ad-IFNalpha without Syn3 was ineffective. Surprisingly, in vitro, Ad-IFNalpha also caused caspase-dependent death of bladder cancer cell lines that were resistant to high concentrations of IFN-alpha protein, including the cell line used in vivo. These findings demonstrate that Ad-IFNalpha can overcome resistance to IFN-alpha protein both in vitro and in vivo and support evaluation of intravesical Ad-IFNalpha/Syn3 for the treatment of superficial bladder ca...Continue Reading

References

May 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·M StreuliC Weissmann
May 23, 1998·The Journal of Urology·A S BelldegrunR D Williams
Mar 4, 2000·The Urologic Clinics of North America·G Dalbagni, H W Herr
Jul 7, 2001·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·C M AhmedJ A Howe
Jun 14, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lance C PagliaroColin P Dinney

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Citations

Aug 8, 2006·Molecular Pharmaceutics·Pradeep TyagiLeaf Huang
Dec 28, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Elena V ShashkovaKonstantin Doronin
May 7, 2010·Current Oncology Reports·Arlene Siefker-Radtke
Feb 16, 2013·Seminars in Cancer Biology·Erik L BrincksThomas S Griffith
Jun 10, 2015·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Úrsula A RossiGerardo C Glikin
Feb 20, 2007·Molecular Aspects of Medicine·Sonia MinuzzoAlberto Amadori
Dec 2, 2015·Therapeutic Advances in Urology·Dominic H Tang, Sam S Chang
Jun 22, 2016·Investigative and Clinical Urology·Thenappan Chandrasekar, Christopher P Evans
Dec 4, 2009·International Journal of Cancer. Journal International Du Cancer·Kai-xin ZhangPaul S Rennie
Aug 2, 2008·Current Opinion in Urology·Bernard H Bochner
Mar 9, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Igor de Luna VieiraBryan E Strauss
Aug 24, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Neal D ShoreColin P N Dinney
Sep 12, 2020·Expert Review of Anticancer Therapy·Mohamad MoussaWajih Saad
May 26, 2017·Biomedicines·Jing Li HuangMasato Yamamoto
Nov 12, 2018·World Journal of Urology·Jonathan J DupliseaColin P Dinney
Dec 3, 2009·Cancer Prevention Research·David J McConkey, Colin P Dinney
Jul 1, 2021·Expert Review of Clinical Pharmacology·Michael Ahdoot, Dan Theodorescu
Oct 13, 2021·Expert Opinion on Therapeutic Targets·Pratishtha GuptaMinal Garg
Nov 13, 2021·Future Oncology·Samantha R Unsworth-WhiteRichard T Bryan

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