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 language | English (US) |
|---|---|
| Pages (from-to) | 336-341 |
| Number of pages | 6 |
| Journal | Cancer Gene Therapy |
| Volume | 20 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2013 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model
AU - Yin, D.
AU - Zhai, Y.
AU - Gruber, H. E.
AU - Ibanez, C. E.
AU - Robbins, J. M.
AU - Kells, A. P.
AU - Kasahara, Noriyuki
AU - Forsayeth, J.
AU - Jolly, D. J.
AU - Bankiewicz, K. S.
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
KW - 5-fluorouracil
KW - convection-enhanced delivery
KW - glioma
KW - RRV
UR - http://www.scopus.com/inward/record.url?scp=84879421222&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879421222&partnerID=8YFLogxK
U2 - 10.1038/cgt.2013.25
DO - 10.1038/cgt.2013.25
M3 - Article
C2 - 23703472
AN - SCOPUS:84879421222
VL - 20
SP - 336
EP - 341
JO - Cancer Gene Therapy
JF - Cancer Gene Therapy
SN - 0929-1903
IS - 6
ER -