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

TitleEffective melanoma immunotherapy with interleukin-2 delivered by a novel polymeric nanoparticle
Authors
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/
Citation
Molecular Cancer Therapeutics, 2011, v. 10 n. 6, p. 1082-1092 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/139027
ISSN
2014 Impact Factor: 5.683
2013 SCImago Journal Rankings: 3.117
ISI Accession Number ID
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).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorYao, Hen_HK
dc.contributor.authorNg, SSen_HK
dc.contributor.authorHuo, LFen_HK
dc.contributor.authorChow, BKCen_HK
dc.contributor.authorShen, Zen_HK
dc.contributor.authorYang, Men_HK
dc.contributor.authorSze, Jen_HK
dc.contributor.authorKo, Oen_HK
dc.contributor.authorLi, Men_HK
dc.contributor.authorYue, Aen_HK
dc.contributor.authorLu, LWen_HK
dc.contributor.authorBian, XWen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorLin, MCen_HK
dc.date.accessioned2011-09-23T05:44:15Z-
dc.date.available2011-09-23T05:44:15Z-
dc.date.issued2011en_HK
dc.identifier.citationMolecular Cancer Therapeutics, 2011, v. 10 n. 6, p. 1082-1092en_HK
dc.identifier.issn1535-7163en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139027-
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.en_HK
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://mct.aacrjournals.org/en_HK
dc.relation.ispartofMolecular Cancer Therapeuticsen_HK
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 nanoparticleen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1535-7163&volume=10&spage=1082&epage=1092&date=2011&atitle=Effective+melanoma+immunotherapy+with+interleukin-2+delivered+by+a+novel+polymeric+nanoparticle-
dc.identifier.emailNg, SS: ssmng@hku.hken_HK
dc.identifier.emailChow, BKC: bkcc@hku.hken_HK
dc.identifier.emailLu, LW: liweilu@hkucc.hku.hken_HK
dc.identifier.emailLin, MC: mcllin@hkucc.hku.hken_HK
dc.identifier.authorityNg, SS=rp00767en_HK
dc.identifier.authorityChow, BKC=rp00681en_HK
dc.identifier.authorityLu, LW=rp00477en_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1535-7163.MCT-10-0717en_HK
dc.identifier.pmid21518728en_HK
dc.identifier.scopuseid_2-s2.0-79958749886en_HK
dc.identifier.hkuros196587en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79958749886&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume10en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1082en_HK
dc.identifier.epage1092en_HK
dc.identifier.isiWOS:000291428000016-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectDevelopment of Novel Nanopolymers for Cancer Gene Therapy-
dc.identifier.scopusauthoridYao, H=13104506400en_HK
dc.identifier.scopusauthoridNg, SS=7403358718en_HK
dc.identifier.scopusauthoridHuo, LF=9275343500en_HK
dc.identifier.scopusauthoridChow, BKC=7102826193en_HK
dc.identifier.scopusauthoridShen, Z=35759640300en_HK
dc.identifier.scopusauthoridYang, M=35228247800en_HK
dc.identifier.scopusauthoridSze, J=7003867625en_HK
dc.identifier.scopusauthoridKo, O=8119962000en_HK
dc.identifier.scopusauthoridLi, M=36066390600en_HK
dc.identifier.scopusauthoridYue, A=54781003500en_HK
dc.identifier.scopusauthoridLu, LW=7403963552en_HK
dc.identifier.scopusauthoridBian, XW=7103023096en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridLin, MC=7404816359en_HK

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