Article: Effective melanoma immunotherapy with interleukin-2 delivered by a novel polymeric nanoparticle
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- Publisher Website: 10.1158/1535-7163.MCT-10-0717
- Scopus: eid_2-s2.0-79958749886
- PMID: 21518728
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| Title | Effective melanoma immunotherapy with interleukin-2 delivered by a novel polymeric nanoparticle | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Authors | Yao, H1 3 4 Ng, SS1 Huo, LF4 Chow, BKC1 Shen, Z2 4 Yang, M1 Sze, J1 4 Ko, O1 Li, M4 Yue, A4 Lu, LW1 Bian, XW3 Kung, HF3 4 Lin, MC1 4 | ||||||||
| Keywords | Animal experiment Antineoplastic activity Blood level Cancer inhibition Cancer survival | ||||||||
| Issue Date | 2011 | ||||||||
| Publisher | American Association for Cancer Research. The Journal's web site is located at http://mct.aacrjournals.org/ | ||||||||
| Citation | Molecular Cancer Therapeutics, 2011, v. 10 n. 6, p. 1082-1092 [How to Cite?] DOI: http://dx.doi.org/10.1158/1535-7163.MCT-10-0717 | ||||||||
| 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 × 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. ©2011 AACR. | ||||||||
| ISSN | 1535-7163 2011 Impact Factor: 5.226 2011 SCImago Journal Rankings: 0.740 | ||||||||
| DOI | http://dx.doi.org/10.1158/1535-7163.MCT-10-0717 | ||||||||
| ISI Accession Number ID | WOS:000291428000016
Funding Information: The work was supported by the funding from the Innovation and Technology Fund (ITS/243/09 to M.C. Lin and S.S. Ng) of the Government of the Hong Kong Special Administrative Region, the National Natural Science Foundation of China (PC: 81001023), and the Natural Science Foundation of ChongQing (CSPC: 2010BC5007). | ||||||||
| References | References in Scopus | ||||||||
| Grants | Development of Novel Nanopolymers for Cancer Gene Therapy |
| dc.contributor.author | Yao, H | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Ng, SS | ||||||||
| dc.contributor.author | Huo, LF | ||||||||
| dc.contributor.author | Chow, BKC | ||||||||
| dc.contributor.author | Shen, Z | ||||||||
| dc.contributor.author | Yang, M | ||||||||
| dc.contributor.author | Sze, J | ||||||||
| dc.contributor.author | Ko, O | ||||||||
| dc.contributor.author | Li, M | ||||||||
| dc.contributor.author | Yue, A | ||||||||
| dc.contributor.author | Lu, LW | ||||||||
| dc.contributor.author | Bian, XW | ||||||||
| dc.contributor.author | Kung, HF | ||||||||
| dc.contributor.author | Lin, MC | ||||||||
| dc.date.accessioned | 2011-09-23T05:44:15Z | ||||||||
| dc.date.available | 2011-09-23T05:44:15Z | ||||||||
| dc.date.issued | 2011 | ||||||||
| dc.description.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 × 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. ©2011 AACR. | ||||||||
| dc.description.grant | Development of Novel Nanopolymers for Cancer Gene Therapy | ||||||||
| dc.description.grantcode | 102599 | ||||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||||
| dc.identifier.citation | Molecular Cancer Therapeutics, 2011, v. 10 n. 6, p. 1082-1092 [How to Cite?] DOI: http://dx.doi.org/10.1158/1535-7163.MCT-10-0717 | ||||||||
| dc.identifier.doi | http://dx.doi.org/10.1158/1535-7163.MCT-10-0717 | ||||||||
| dc.identifier.epage | 1092 | ||||||||
| dc.identifier.hkuros | 196587 | ||||||||
| dc.identifier.isi | WOS:000291428000016
Funding Information: The work was supported by the funding from the Innovation and Technology Fund (ITS/243/09 to M.C. Lin and S.S. Ng) of the Government of the Hong Kong Special Administrative Region, the National Natural Science Foundation of China (PC: 81001023), and the Natural Science Foundation of ChongQing (CSPC: 2010BC5007). | ||||||||
| dc.identifier.issn | 1535-7163 2011 Impact Factor: 5.226 2011 SCImago Journal Rankings: 0.740 | ||||||||
| dc.identifier.issue | 6 | ||||||||
| dc.identifier.openurl | | ||||||||
| dc.identifier.pmid | 21518728 | ||||||||
| dc.identifier.scopus | eid_2-s2.0-79958749886 | ||||||||
| dc.identifier.spage | 1082 | ||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/139027 | ||||||||
| dc.identifier.volume | 10 | ||||||||
| dc.language | eng | ||||||||
| dc.publisher | American Association for Cancer Research. The Journal's web site is located at http://mct.aacrjournals.org/ | ||||||||
| dc.publisher.place | United States | ||||||||
| dc.relation.ispartof | Molecular Cancer Therapeutics | ||||||||
| dc.relation.references | References in Scopus | ||||||||
| dc.subject | Animal experiment | ||||||||
| dc.subject | Antineoplastic activity | ||||||||
| dc.subject | Blood level | ||||||||
| dc.subject | Cancer inhibition | ||||||||
| dc.subject | Cancer survival | ||||||||
| dc.title | Effective melanoma immunotherapy with interleukin-2 delivered by a novel polymeric nanoparticle | ||||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Shanghai Jiaotong University
- Third Military Medical University
- Chinese University of Hong Kong