title: Antitumor activity of tumor-targeted RNA replicase-based plasmid that expresses interleukin-2 in a murine melanoma model.
abstract: 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-β, 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-β 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-β 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-β. The RNA replicase-based, IL2-expressing plasmid may have applications in melanoma gene therapy.
authors: Pharmaceutics Division, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, USA.
authors: B Leticia
authors: BL
authors: Rodriguez
authors: Jorge M
authors: JM
authors: Blando
authors: Dharmika S P
authors: DS
authors: Lansakara-P
authors: Yuriko
authors: Y
authors: Kiguchi
authors: John
authors: J
authors: DiGiovanni
authors: Zhengrong
authors: Z
authors: Cui
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005260:Female; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry; D008545:Melanoma / Q000378:metabolism* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D008081:Liposomes; D012324:RNA-Dependent RNA Polymerase; D053148:Caspase 3
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