Highly efficient gene delivery for bladder cancers by intravesically administered replication-competent retroviral vectors

Eiji Kikuchi, Silvia Menendez, Choichiro Ozu, Makoto Ohori, Carlos Cordon-Cardo, Christopher R. Logg, Noriyuki Kasahara, Bernard H. Bochner

研究成果: Article査読

22 被引用数 (Scopus)

抄録

Purpose: In an attempt to improve viral delivery of potentially therapeutic genes via an intravesical route, we have recently developed murine leukemia virus-based replication-competent retrovirus (RCR) vectors. Experimental Design: We evaluated the transduction efficiency of intravesically administered RCR vectors to bladder tumor using orthotopic animal models to determine their potential as delivery vectors for bladder cancer. Results: The RCR vector containing green fluorescent protein (GFP) marker gene achieved efficient in vitro transmission of the GFP transgene. Murine bladder tumor-2 mouse bladder tumors exposed to intravesically administered RCR vectors exhibited 0%, 9.2 ± 2.9%, and 30.0 ± 6.2% of GFP expression at 9, 18, and 27 days after exposure in the orthotopic model, respectively. Orthotopic KU-19-19 human bladder tumors exposed to intravesically administered RCR vectors exhibited 3%, 85 ± 1.0%, and 100% of GFP expression at 7, 21, and 35 days after exposure, respectively. GFP staining was observed only in the tumor cells in the bladder. No detectable PCR products of GFP gene could be observed in distant organs. Treatment with RCR vectors containing yeast cytosine deaminase (CD) gene plus 5-fluorocytosine (5-FC) dramatically inhibited the growth of preestablished murine bladder tumor-2 tumors. A single course of 5-FC treatment resulted in a 50% animal survival in mice exposed to RCR-CD compared with a 0% survival in all controls over a 70-day follow-up period. Conclusions: Intravesically administered RCR vectors can efficiently deliver genes to orthotopic bladder tumor without viral spread in distant organs. RCR-CD/5-FC suicide gene therapy promises to be a novel and potentially therapeutic modality for bladder cancer.

本文言語English
ページ(範囲)4511-4518
ページ数8
ジャーナルClinical Cancer Research
13
15
DOI
出版ステータスPublished - 2007 8月 1

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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