Antitumor Activity of Tumor-Targeted RNA Replicase-Based Plasmid That Expresses Interleukin-2 in a Murine Melanoma Model

作者：Rodriguez B Leticia; Blando Jorge M; Lansakara P Dharmika S P; Kiguchi Yuriko; DiGiovanni John; Cui Zhengrong^*

来源：Molecular Pharmaceutics, 2013, 10(6): 2404-2415.

DOI：10.1021/mp400033m

• dsRNA therapy
• sigma receptor
• anisamide
• IL2 therapy
• melanoma

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-beta 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-beta plasmid by incorporating interleukin-2 (112) 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 1316 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-beta plasmid at controlling the growth of B16 melanoma in mice, and 1316 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-beta. The RNA replicase-based, IL2-expressing plasmid may have applications in melanoma gene therapy.

• 出版日期2013-6