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000139134 0247_ $$2doi$$a10.1016/j.jconrel.2017.01.004
000139134 0247_ $$2pmid$$apmid:28069554
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000139134 0247_ $$2ISSN$$a1873-4995
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000139134 037__ $$aDZNE-2020-05456
000139134 041__ $$aEnglish
000139134 082__ $$a610
000139134 1001_ $$aBayyurt, Banu$$b0
000139134 245__ $$aEncapsulation of two different TLR ligands into liposomes confer protective immunity and prevent tumor development.
000139134 260__ $$aNew York, NY [u.a.]$$bElsevier$$c2017
000139134 264_1 $$2Crossref$$3print$$bElsevier BV$$c2017-02-01
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000139134 520__ $$aNucleic acid-based Toll-like receptor (TLR) ligands are promising adjuvants and immunotherapeutic agents. Combination of TLR ligands potentiates immune response by providing synergistic immune activity via triggering different signaling pathways and may impact antigen dependent T-cell immune memory. However, their short circulation time due to nuclease attack hampers their clinical performance. Liposomes offer inclusion of protein and nucleic acid-based drugs with high encapsulation efficiency and drug loading. Furthermore, they protect cargo from enzymatic cleavage while providing stability, and enhancing biological activity. Herein, we aimed to develop a liposomal carrier system co-encapsulating TLR3 (polyinosinic-polycytidylic acid; poly(I:C)) and TLR9 (oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs; CpG ODN) ligands as immunoadjuvants together with protein antigen. To demonstrate that this depot system not only induce synergistic innate immune activation but also boost antigen-dependent immune response, we analyzed the potency of dual ligand encapsulated liposomes in long-term cancer protection assay. Data revealed that CpG ODN and poly(I:C) co-encapsulation significantly enhanced cytokine production from spleen cells. Activation and maturation of dendritic cells as well as bactericidal potency of macrophages along with internalization capacity of ligands were elevated upon incubation with liposomes co-encapsulating CpG ODN and poly(I:C). Immunization with co-encapsulated liposomes induced OVA-specific Th1-biased immunity which persisted for eight months post-booster injection. Subsequent challenge with OVA-expressing tumor cell line, E.G7, demonstrated that mice immunized with liposomes co-encapsulating dual ligands had significantly slower tumor progression. Tumor clearance was dependent on OVA-specific cytotoxic memory T-cells. These results suggest that liposomes co-encapsulating TLR3 and TLR9 ligands and a specific cancer antigen could be developed as a preventive cancer vaccine.
000139134 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000139134 542__ $$2Crossref$$i2017-02-01$$uhttps://www.elsevier.com/tdm/userlicense/1.0/
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000139134 650_7 $$2NLM Chemicals$$aAdjuvants, Immunologic
000139134 650_7 $$2NLM Chemicals$$aCPG-oligonucleotide
000139134 650_7 $$2NLM Chemicals$$aCancer Vaccines
000139134 650_7 $$2NLM Chemicals$$aInterleukin-6
000139134 650_7 $$2NLM Chemicals$$aLiposomes
000139134 650_7 $$2NLM Chemicals$$aOligodeoxyribonucleotides
000139134 650_7 $$2NLM Chemicals$$aToll-Like Receptor 3
000139134 650_7 $$2NLM Chemicals$$aToll-Like Receptor 9
000139134 650_7 $$09008-11-1$$2NLM Chemicals$$aInterferons
000139134 650_7 $$0O84C90HH2L$$2NLM Chemicals$$aPoly I-C
000139134 650_2 $$2MeSH$$aAdjuvants, Immunologic: administration & dosage
000139134 650_2 $$2MeSH$$aAdjuvants, Immunologic: pharmacology
000139134 650_2 $$2MeSH$$aAdjuvants, Immunologic: therapeutic use
000139134 650_2 $$2MeSH$$aAnimals
000139134 650_2 $$2MeSH$$aCancer Vaccines: administration & dosage
000139134 650_2 $$2MeSH$$aCancer Vaccines: pharmacology
000139134 650_2 $$2MeSH$$aCancer Vaccines: therapeutic use
000139134 650_2 $$2MeSH$$aFemale
000139134 650_2 $$2MeSH$$aImmunity: drug effects
000139134 650_2 $$2MeSH$$aImmunization
000139134 650_2 $$2MeSH$$aInterferons: immunology
000139134 650_2 $$2MeSH$$aInterleukin-6: immunology
000139134 650_2 $$2MeSH$$aLiposomes: chemistry
000139134 650_2 $$2MeSH$$aMice
000139134 650_2 $$2MeSH$$aMice, Inbred C57BL
000139134 650_2 $$2MeSH$$aNeoplasms: immunology
000139134 650_2 $$2MeSH$$aNeoplasms: prevention & control
000139134 650_2 $$2MeSH$$aOligodeoxyribonucleotides: administration & dosage
000139134 650_2 $$2MeSH$$aOligodeoxyribonucleotides: pharmacology
000139134 650_2 $$2MeSH$$aOligodeoxyribonucleotides: therapeutic use
000139134 650_2 $$2MeSH$$aPoly I-C: administration & dosage
000139134 650_2 $$2MeSH$$aPoly I-C: pharmacology
000139134 650_2 $$2MeSH$$aPoly I-C: therapeutic use
000139134 650_2 $$2MeSH$$aRAW 264.7 Cells
000139134 650_2 $$2MeSH$$aToll-Like Receptor 3: immunology
000139134 650_2 $$2MeSH$$aToll-Like Receptor 9: immunology
000139134 7001_ $$0P:(DE-2719)9000945$$aTincer, Gizem$$b1$$udzne
000139134 7001_ $$aAlmacioglu, Kubra$$b2
000139134 7001_ $$aAlpdundar, Esin$$b3
000139134 7001_ $$aGursel, Mayda$$b4
000139134 7001_ $$0P:(DE-HGF)0$$aGursel, Ihsan$$b5$$eCorresponding author
000139134 77318 $$2Crossref$$3journal-article$$a10.1016/j.jconrel.2017.01.004$$b : Elsevier BV, 2017-02-01$$p134-144$$tJournal of Controlled Release$$v247$$x0168-3659$$y2017
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000139134 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000945$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b1$$kDZNE
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