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Article: Effective melanoma immunotherapy with interleukin-2 delivered by a novel polymeric nanoparticle
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TitleEffective melanoma immunotherapy with interleukin-2 delivered by a novel polymeric nanoparticle
 
AuthorsYao, H3 1 4
Ng, SS1
Huo, LF4
Chow, BKC1
Shen, Z4 2
Yang, M1
Sze, J1 4
Ko, O1
Li, M4
Yue, A4
Lu, LW1
Bian, XW3
Kung, HF3 4
Lin, MC1 4
 
KeywordsAnimal experiment
Antineoplastic activity
Blood level
Cancer inhibition
Cancer survival
 
Issue Date2011
 
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://mct.aacrjournals.org/
 
CitationMolecular 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
 
AbstractInterleukin-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.
 
ISSN1535-7163
2012 Impact Factor: 5.599
2012 SCImago Journal Rankings: 2.387
 
DOIhttp://dx.doi.org/10.1158/1535-7163.MCT-10-0717
 
ISI Accession Number IDWOS:000291428000016
Funding AgencyGrant Number
Government of the Hong Kong Special Administrative RegionITS/243/09
National Natural Science Foundation of ChinaPC: 81001023
Natural Science Foundation of ChongQingCSPC: 2010BC5007
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).

 
ReferencesReferences in Scopus
 
GrantsDevelopment of Novel Nanopolymers for Cancer Gene Therapy
 
DC FieldValue
dc.contributor.authorYao, H
 
dc.contributor.authorNg, SS
 
dc.contributor.authorHuo, LF
 
dc.contributor.authorChow, BKC
 
dc.contributor.authorShen, Z
 
dc.contributor.authorYang, M
 
dc.contributor.authorSze, J
 
dc.contributor.authorKo, O
 
dc.contributor.authorLi, M
 
dc.contributor.authorYue, A
 
dc.contributor.authorLu, LW
 
dc.contributor.authorBian, XW
 
dc.contributor.authorKung, HF
 
dc.contributor.authorLin, MC
 
dc.date.accessioned2011-09-23T05:44:15Z
 
dc.date.available2011-09-23T05:44:15Z
 
dc.date.issued2011
 
dc.description.abstractInterleukin-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.natureLink_to_subscribed_fulltext
 
dc.identifier.citationMolecular 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.doihttp://dx.doi.org/10.1158/1535-7163.MCT-10-0717
 
dc.identifier.epage1092
 
dc.identifier.hkuros196587
 
dc.identifier.isiWOS:000291428000016
Funding AgencyGrant Number
Government of the Hong Kong Special Administrative RegionITS/243/09
National Natural Science Foundation of ChinaPC: 81001023
Natural Science Foundation of ChongQingCSPC: 2010BC5007
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.issn1535-7163
2012 Impact Factor: 5.599
2012 SCImago Journal Rankings: 2.387
 
dc.identifier.issue6
 
dc.identifier.openurl
 
dc.identifier.pmid21518728
 
dc.identifier.scopuseid_2-s2.0-79958749886
 
dc.identifier.spage1082
 
dc.identifier.urihttp://hdl.handle.net/10722/139027
 
dc.identifier.volume10
 
dc.languageeng
 
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://mct.aacrjournals.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofMolecular Cancer Therapeutics
 
dc.relation.projectDevelopment of Novel Nanopolymers for Cancer Gene Therapy
 
dc.relation.referencesReferences in Scopus
 
dc.subjectAnimal experiment
 
dc.subjectAntineoplastic activity
 
dc.subjectBlood level
 
dc.subjectCancer inhibition
 
dc.subjectCancer survival
 
dc.titleEffective melanoma immunotherapy with interleukin-2 delivered by a novel polymeric nanoparticle
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Shanghai Jiaotong University
  3. Third Military Medical University
  4. Chinese University of Hong Kong