001     139134
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024 7 _ |a 10.1016/j.jconrel.2017.01.004
|2 doi
024 7 _ |a pmid:28069554
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024 7 _ |a 0168-3659
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024 7 _ |a 1873-4995
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024 7 _ |a altmetric:16309064
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037 _ _ |a DZNE-2020-05456
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Bayyurt, Banu
|b 0
245 _ _ |a Encapsulation of two different TLR ligands into liposomes confer protective immunity and prevent tumor development.
260 _ _ |a New York, NY [u.a.]
|c 2017
|b Elsevier
264 _ 1 |3 print
|2 Crossref
|b Elsevier BV
|c 2017-02-01
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Nucleic 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.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
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|f POF III
|x 0
542 _ _ |i 2017-02-01
|2 Crossref
|u https://www.elsevier.com/tdm/userlicense/1.0/
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Adjuvants, Immunologic
|2 NLM Chemicals
650 _ 7 |a CPG-oligonucleotide
|2 NLM Chemicals
650 _ 7 |a Cancer Vaccines
|2 NLM Chemicals
650 _ 7 |a Interleukin-6
|2 NLM Chemicals
650 _ 7 |a Liposomes
|2 NLM Chemicals
650 _ 7 |a Oligodeoxyribonucleotides
|2 NLM Chemicals
650 _ 7 |a Toll-Like Receptor 3
|2 NLM Chemicals
650 _ 7 |a Toll-Like Receptor 9
|2 NLM Chemicals
650 _ 7 |a Interferons
|0 9008-11-1
|2 NLM Chemicals
650 _ 7 |a Poly I-C
|0 O84C90HH2L
|2 NLM Chemicals
650 _ 2 |a Adjuvants, Immunologic: administration & dosage
|2 MeSH
650 _ 2 |a Adjuvants, Immunologic: pharmacology
|2 MeSH
650 _ 2 |a Adjuvants, Immunologic: therapeutic use
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Cancer Vaccines: administration & dosage
|2 MeSH
650 _ 2 |a Cancer Vaccines: pharmacology
|2 MeSH
650 _ 2 |a Cancer Vaccines: therapeutic use
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Immunity: drug effects
|2 MeSH
650 _ 2 |a Immunization
|2 MeSH
650 _ 2 |a Interferons: immunology
|2 MeSH
650 _ 2 |a Interleukin-6: immunology
|2 MeSH
650 _ 2 |a Liposomes: chemistry
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Neoplasms: immunology
|2 MeSH
650 _ 2 |a Neoplasms: prevention & control
|2 MeSH
650 _ 2 |a Oligodeoxyribonucleotides: administration & dosage
|2 MeSH
650 _ 2 |a Oligodeoxyribonucleotides: pharmacology
|2 MeSH
650 _ 2 |a Oligodeoxyribonucleotides: therapeutic use
|2 MeSH
650 _ 2 |a Poly I-C: administration & dosage
|2 MeSH
650 _ 2 |a Poly I-C: pharmacology
|2 MeSH
650 _ 2 |a Poly I-C: therapeutic use
|2 MeSH
650 _ 2 |a RAW 264.7 Cells
|2 MeSH
650 _ 2 |a Toll-Like Receptor 3: immunology
|2 MeSH
650 _ 2 |a Toll-Like Receptor 9: immunology
|2 MeSH
700 1 _ |a Tincer, Gizem
|0 P:(DE-2719)9000945
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700 1 _ |a Almacioglu, Kubra
|b 2
700 1 _ |a Alpdundar, Esin
|b 3
700 1 _ |a Gursel, Mayda
|b 4
700 1 _ |a Gursel, Ihsan
|0 P:(DE-HGF)0
|b 5
|e Corresponding author
773 1 8 |a 10.1016/j.jconrel.2017.01.004
|b : Elsevier BV, 2017-02-01
|p 134-144
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|t Journal of Controlled Release
|v 247
|y 2017
|x 0168-3659
773 _ _ |a 10.1016/j.jconrel.2017.01.004
|g Vol. 247, p. 134 - 144
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|q 247<134 - 144
|p 134-144
|t Journal of controlled release
|v 247
|y 2017
|x 0168-3659
856 4 _ |u https://pub.dzne.de/record/139134/files/DZNE-2020-05456_Restricted.pdf
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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913 1 _ |a DE-HGF
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