Antitumor Activity of Tumor-Targeted RNA Replicase-Based Plasmid That Expresses Interleukin-2 in a Murine Melanoma Model
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- 作者：B. Leticia Rodriguez ; Jorge M. Blando ; Dharmika S. P. Lansakara-P ; Yuriko Kiguchi ; John DiGiovanni ; Zhengrong Cui
- 刊名：Molecular Pharmaceutics
- 出版年：2013
- 出版时间：June 3, 2013
- 年：2013
- 卷：10
- 期：6
- 页码：2404-2415
- 全文大小：595K
- 年卷期：v.10,no.6(June 3, 2013)
- ISSN：1543-8392
文摘
Double-stranded RNA (dsRNA) has multiple antitumor mechanisms that may be used to control tumor growth. Previously we have shown that treatment of solid tumors with a plasmid that encodes Sindbis viral RNA replicase complex, pSIN-尾, significantly inhibited the growth of tumors in mice. In the present study, we evaluated the feasibility of further improving the antitumor activity of the pSIN-尾 plasmid by incorporating interleukin-2 (IL2) gene into the plasmid. The resultant pSIN-IL2 plasmid was delivered to mouse melanoma cells that overexpress the sigma receptor. Here we report that the pSIN-IL2 plasmid was more effective at controlling the growth of B16 melanoma in mice when complexed with sigma receptor-targeted liposomes than with the untargeted liposomes. Importantly, the pSIN-IL2 plasmid was more effective than pSIN-尾 plasmid at controlling the growth of B16 melanoma in mice, and B16 tumor-bearing mice that were treated with pSIN-IL2 had an elevated number of activated CD4+, CD8+, and natural killer cells, as compared to those treated with pSIN-尾. The RNA replicase-based, IL2-expressing plasmid may have applications in melanoma gene therapy.