Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model

D. Yin, Y. Zhai, H. E. Gruber, C. E. Ibanez, J. M. Robbins, A. P. Kells, N. Kasahara, J. Forsayeth, D. J. Jolly, K. S. Bankiewicz

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

In the present study, we compared the therapeutic effect of tumor-selective retroviral replicating vectors (RRV) expressing the yeast cytosine deaminase (CD) delivered by convection-enhanced delivery (CED) or simple injection, followed by systemic administration of the pro-drug, 5-fluorocytosine (5-FC). Treatment with RRV-CD and systemic 5-FC significantly increased survival in rodent U87MG glioma model in comparison with controls (P<0.01). Interestingly, CED of RRV-CD followed by 5-FC further enhanced survival in this animal model in comparison with intra-tumoral injection of RRV-CD, followed by systemic 5-FC (P<0.05). High expression levels of Ki-67 were found in untreated tumors compared with treated. Untreated tumors were also much larger than treated. CED resulted in excellent distribution of RRV while only partial distribution of RRV was obtained after injection. Furthermore, RRV-CD and CD were also found in tumors from treated rats at study end points. These results demonstrated that RRV vectors may efficiently transduce and stably propagate in malignant human glioma, thereby achieving a significant in situ amplification effect after initial administration. We conclude that delivery of RRV into the glioma by CED provides much wider vector distribution than simple injection, and this correlated with better therapeutic outcomes.

Original languageEnglish (US)
Pages (from-to)336-341
Number of pages6
JournalCancer gene therapy
Volume20
Issue number6
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

Keywords

  • 5-fluorouracil
  • RRV
  • convection-enhanced delivery
  • glioma

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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    Yin, D., Zhai, Y., Gruber, H. E., Ibanez, C. E., Robbins, J. M., Kells, A. P., Kasahara, N., Forsayeth, J., Jolly, D. J., & Bankiewicz, K. S. (2013). Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model. Cancer gene therapy, 20(6), 336-341. https://doi.org/10.1038/cgt.2013.25