Effective Melanoma Immunotherapy with Interleukin-2 Delivered by a Novel Polymeric Nanoparticle
2011; American Association for Cancer Research; Volume: 10; Issue: 6 Linguagem: Inglês
10.1158/1535-7163.mct-10-0717
ISSN1538-8514
AutoresHong Yao, Samuel S. Ng, Long-Fei Huo, Bkc Chow, Zan Shen, Min Yang, Johnny Sze, Otis King Hung Ko, Ming Li, Alexander Yue, Liwei Lu, Xiu‐Wu Bian, Hsiang‐Fu Kung, Marie C.M. Lin,
Tópico(s)Immunotherapy and Immune Responses
ResumoInterleukin-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 (600 Da) 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 × 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.
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