Replication-competent retrovirus vector-mediated prodrug activator gene therapy in experimental models of human malignant mesothelioma

Y. Kawasaki, A. Tamamoto, M. Takagi-Kimura, Y. Maeyama, N. Yamaoka, N. Terada, H. Okamura, Noriyuki Kasahara, S. Kubo

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Replication-competent retrovirus (RCR) vectors have been shown to achieve significantly enhanced tumor transduction efficiency and therapeutic efficacy in various cancer models. In the present study, we investigated RCR vector-mediated prodrug activator gene therapy for the treatment of malignant mesothelioma, a highly aggressive tumor with poor prognosis. RCR-GFP vector expressing the green fluorescent protein marker gene successfully infected and efficiently replicated in human malignant mesothelioma cell lines, as compared with non-malignant mesothelial cells in vitro. In mice with pre-established subcutaneous tumor xenografts, RCR-GFP vector showed robust spread throughout entire tumor masses after intratumoral administration. Next, RCR-cytosine deaminase (RCR-CD), expressing the yeast CD prodrug activator gene, showed efficient transmission of the prodrug activator gene associated with replicative spread of the virus, resulting in efficient killing of malignant mesothelioma cells in a prodrug 5-fluorocytosine (5FC)-dose dependent manner in vitro. After a single intratumoral injection of RCR-CD followed by intraperitoneal administration of 5FC, RCR vector-mediated prodrug activator gene therapy achieved significant inhibition of subcutaneous tumor growth, and significantly prolonged survival in the disseminated peritoneal model of malignant mesothelioma. These data indicate the potential utility of RCR vector-mediated prodrug activator gene therapy in the treatment of malignant mesothelioma.

Original languageEnglish (US)
Pages (from-to)571-578
Number of pages8
JournalCancer Gene Therapy
Volume18
Issue number8
DOIs
StatePublished - Aug 2011
Externally publishedYes

Fingerprint

Prodrugs
Retroviridae
Genetic Therapy
Theoretical Models
Flucytosine
Neoplasms
Cytosine Deaminase
Genes
Malignant Mesothelioma
Green Fluorescent Proteins
Heterografts
Therapeutics
Yeasts
Viruses
Cell Line
Injections
Survival
Growth

Keywords

  • malignant mesothelioma
  • molecular imaging
  • prodrug activator gene therapy
  • replication-competent retrovirus vector

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology

Cite this

Kawasaki, Y., Tamamoto, A., Takagi-Kimura, M., Maeyama, Y., Yamaoka, N., Terada, N., ... Kubo, S. (2011). Replication-competent retrovirus vector-mediated prodrug activator gene therapy in experimental models of human malignant mesothelioma. Cancer Gene Therapy, 18(8), 571-578. https://doi.org/10.1038/cgt.2011.25

Replication-competent retrovirus vector-mediated prodrug activator gene therapy in experimental models of human malignant mesothelioma. / Kawasaki, Y.; Tamamoto, A.; Takagi-Kimura, M.; Maeyama, Y.; Yamaoka, N.; Terada, N.; Okamura, H.; Kasahara, Noriyuki; Kubo, S.

In: Cancer Gene Therapy, Vol. 18, No. 8, 08.2011, p. 571-578.

Research output: Contribution to journalArticle

Kawasaki, Y, Tamamoto, A, Takagi-Kimura, M, Maeyama, Y, Yamaoka, N, Terada, N, Okamura, H, Kasahara, N & Kubo, S 2011, 'Replication-competent retrovirus vector-mediated prodrug activator gene therapy in experimental models of human malignant mesothelioma', Cancer Gene Therapy, vol. 18, no. 8, pp. 571-578. https://doi.org/10.1038/cgt.2011.25
Kawasaki, Y. ; Tamamoto, A. ; Takagi-Kimura, M. ; Maeyama, Y. ; Yamaoka, N. ; Terada, N. ; Okamura, H. ; Kasahara, Noriyuki ; Kubo, S. / Replication-competent retrovirus vector-mediated prodrug activator gene therapy in experimental models of human malignant mesothelioma. In: Cancer Gene Therapy. 2011 ; Vol. 18, No. 8. pp. 571-578.
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