Treatment of Melanoma by a Novel Non-Viral Vector Mediated Delivery of Interleukin-2

Abstract

a cytokine showed the best anti-tumor activity in patients with malignant melanoma. However, the short half-life of IL-2 protein in serum requires repeated high doses, resulting in severe side effects. Here we reported a novel polycationnic vectors H1, which consists of low molecular weight polyethylenimine(PEI 600Da) linked by Cyclodextrin and conjugated with folate acid(named H1). We found that H1-mediated transfection of plasmid encoding IL-2(H1/IL-2) could suppress tumor growth and prolong survival of the melanoma tumor bearing mice. We showed that immune cells, including CTL and NK cells, play critical roles for antitumor effects of H1/IL-2. Importantly, the antitumor effects produced by repeated H1/IL-2 (50ug) injections were comparable to that of adenovirus carrying IL-2 (Adv-IL2, 2×108 pfu). Moreover, the numbers of CD4+CD25+ Treg cells in peripheral blood of the mice repeatedly injected with a high dose of H1/IL-2 were not augmented as compared with the control group. In conclusion, these results demonstrated that H1-mediated IL-2 plasmid transfection induces anti-tumor effects comparable to that of Adv-IL-2 with higher safety and thus represents an alternative gene therapeutic strategy for melanoma.