Effective melanoma immunotherapy with interleukin-2 delivered by a novel polymeric nanoparticle

Hong Yao, Samuel S. Ng, Long Fei Huo, Billy K.C. Chow, Zan Shen, Min Yang, Johnny Sze, Otis Ko, Ming Li, Alexander Yue, Li Wei Lu, Xiu Wu Bian, Hsiang Fu Kung, Marie C. Lin

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Interleukin-2 (IL-2) has been shown to possess antitumor activity in numerous preclinical and clinical studies. However, the short half-life of recombinant IL-2 protein in serum requires repeated high-dose injections, resulting in severe side effects. Although adenovirus-mediated IL-2 gene therapy has shown antitumor efficacy, the host antibody response to adenoviral particles and potential biosafety concerns still obstruct its clinical applications. Here we report a novel nanopolymer for IL-2 delivery, consisting of low molecular weight polyethylenimine (600Da) linked by β-cyclodextrin and conjugated with folate (named H1). H1 was mixed with IL-2 plasmid to form H1/pIL-2 polyplexes of around 100 nm in diameter. Peritumoral injection of these polyplexes suppressed the tumor growth and prolonged the survival of C57/BL6 mice bearing B16-F1 melanoma grafts. Importantly, the antitumor effects of H1/pIL-2 (50 μg DNA) were similar to those of recombinant adenoviruses expressing IL-2 (rAdv-IL-2; 2 × 108 pfu). Furthermore, we showed that H1/pIL-2 stimulated the activation and proliferation of CD8+, CD4+ T cell, and natural killer cells in peripheral blood and increased the infiltration of CD8+, CD4+ Tcells, and natural killer cells into the tumor environment. In conclusion, these results show that H1/pIL-2 is an effective and safe melanoma therapeutic with an efficacy comparable to that of rAdv-IL-2. This treatment represents an alternative gene therapy strategy for melanoma.

Original languageEnglish (US)
Pages (from-to)1082-1092
Number of pages11
JournalMolecular Cancer Therapeutics
Volume10
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

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