Encapsulation of two different TLR ligands into liposomes confer protective immunity and prevent tumor development

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dc.citation.epage144en_US
dc.citation.spage134en_US
dc.citation.volumeNumber247en_US
dc.contributor.authorBayyurt, B.en_US
dc.contributor.authorTincer, G.en_US
dc.contributor.authorAlmacioglu, K.en_US
dc.contributor.authorAlpdundar, E.en_US
dc.contributor.authorGursel, M.en_US
dc.contributor.authorGursel, I.en_US
dc.date.accessioned2018-04-12T11:11:30Z
dc.date.available2018-04-12T11:11:30Z
dc.date.issued2017en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractNucleic 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. � 2017 Elsevier B.V.en_US
dc.identifier.doi10.1016/j.jconrel.2017.01.004en_US
dc.identifier.issn0168-3659
dc.identifier.urihttp://hdl.handle.net/11693/37368
dc.language.isoEnglishen_US
dc.publisherElsevier B.V.en_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.jconrel.2017.01.004en_US
dc.source.titleJournal of Controlled Releaseen_US
dc.subjectImmune responseen_US
dc.subjectImmunoadjuvanten_US
dc.subjectLigandsen_US
dc.subjectLiposomesen_US
dc.subjectPreventive cancer vaccineen_US
dc.subjectTLR3en_US
dc.subjectTLR9en_US
dc.subjectActivation analysisen_US
dc.subjectAntigensen_US
dc.subjectBioactivityen_US
dc.subjectCell cultureen_US
dc.subjectCell signalingen_US
dc.subjectCellsen_US
dc.subjectChemical activationen_US
dc.subjectCytologyen_US
dc.subjectData encapsulationen_US
dc.subjectDiseasesen_US
dc.subjectEncapsulationen_US
dc.subjectImmune systemen_US
dc.subjectImmunizationen_US
dc.subjectLiposomesen_US
dc.subjectNucleic acidsen_US
dc.subjectProteinsen_US
dc.subjectT-cellsen_US
dc.subjectTumorsen_US
dc.subjectVaccinesen_US
dc.titleEncapsulation of two different TLR ligands into liposomes confer protective immunity and prevent tumor developmenten_US
dc.typeArticleen_US

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