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


Authors: Kikuchi, E.; Menendez, S.; Ozu, C.; Ohori, M.; Cordon-Cardo, C.; Logg, C. R.; Kasahara, N.; Bochner, B. H.
Article Title: Highly efficient gene delivery for bladder cancers by intravesically administered replication-competent retroviral vectors
Abstract: 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. © 2007 American Association for Cancer Research.
Keywords: cancer survival; controlled study; protein expression; survival rate; nonhuman; follow up; polymerase chain reaction; animal cell; mouse; animals; mice; animal tissue; gene; green fluorescent protein; animal experiment; animal model; tumor cells, cultured; bladder cancer; urinary bladder neoplasms; viral gene delivery system; genetic vectors; transduction, genetic; mice, nude; gene therapy; retrovirus vector; green fluorescent proteins; plasmids; virus replication; administration, intravesical; transgenes; retroviridae; gene transfer techniques; mice, inbred c3h; cytosine deaminase; flucytosine; cancer gene therapy; suicide gene; antimetabolites; suicide gene therapy; orthotopic transplantation; cd gene; gfp gene; leukemia virus, murine
Journal Title: Clinical Cancer Research
Volume: 13
Issue: 15
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2007-08-01
Start Page: 4511
End Page: 4518
Language: English
DOI: 10.1158/1078-0432.ccr-07-0151
PUBMED: 17671137
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 8" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Eiji Kikuchi
    11 Kikuchi
  2. Choichiro Ozu
    5 Ozu
  3. Makoto Ohori
    50 Ohori
  4. Bernard Bochner
    324 Bochner