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, Noriyuki Kasahara, J. Forsayeth, D. J. Jolly, K. S. Bankiewicz

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 2013
Externally publishedYes

Fingerprint

Cytosine Deaminase
Convection
Brain Neoplasms
Flucytosine
Rodentia
Glioma
Neoplasms
Injections
Survival
Prodrugs
Therapeutic Uses
Animal Models
Yeasts
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology

Cite this

Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model. / Yin, D.; Zhai, Y.; Gruber, H. E.; Ibanez, C. E.; Robbins, J. M.; Kells, A. P.; Kasahara, Noriyuki; Forsayeth, J.; Jolly, D. J.; Bankiewicz, K. S.

In: Cancer Gene Therapy, Vol. 20, No. 6, 06.2013, p. 336-341.

Research output: Contribution to journalArticle

Yin, D, Zhai, Y, Gruber, HE, Ibanez, CE, Robbins, JM, Kells, AP, Kasahara, N, Forsayeth, J, Jolly, DJ & Bankiewicz, KS 2013, 'Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model', Cancer Gene Therapy, vol. 20, no. 6, pp. 336-341. https://doi.org/10.1038/cgt.2013.25
Yin, D. ; Zhai, Y. ; Gruber, H. E. ; Ibanez, C. E. ; Robbins, J. M. ; Kells, A. P. ; Kasahara, Noriyuki ; Forsayeth, J. ; Jolly, D. J. ; Bankiewicz, K. S. / Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model. In: Cancer Gene Therapy. 2013 ; Vol. 20, No. 6. pp. 336-341.
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