Journal
MOLECULAR CANCER THERAPEUTICS
Volume 10, Issue 6, Pages 1082-1092Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-10-0717
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Funding
- Government of the Hong Kong Special Administrative Region [ITS/243/09]
- National Natural Science Foundation of China [PC: 81001023]
- Natural Science Foundation of ChongQing [CSPC: 2010BC5007]
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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 beta-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 mu g DNA) were similar to those of recombinant adenoviruses expressing IL-2 (rAdv-IL-2; 2 x 10(8) 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. Mol Cancer Ther; 10(6); 1082-92. (C)2011 AACR.
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