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@ARTICLE{Bayyurt:139134,
      author       = {Bayyurt, Banu and Tincer, Gizem and Almacioglu, Kubra and
                      Alpdundar, Esin and Gursel, Mayda and Gursel, Ihsan},
      title        = {{E}ncapsulation of two different {TLR} ligands into
                      liposomes confer protective immunity and prevent tumor
                      development.},
      journal      = {Journal of controlled release},
      volume       = {247},
      issn         = {0168-3659},
      address      = {New York, NY [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2020-05456},
      pages        = {134-144},
      year         = {2017},
      abstract     = {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.},
      keywords     = {Adjuvants, Immunologic: administration $\&$ dosage /
                      Adjuvants, Immunologic: pharmacology / Adjuvants,
                      Immunologic: therapeutic use / Animals / Cancer Vaccines:
                      administration $\&$ dosage / Cancer Vaccines: pharmacology /
                      Cancer Vaccines: therapeutic use / Female / Immunity: drug
                      effects / Immunization / Interferons: immunology /
                      Interleukin-6: immunology / Liposomes: chemistry / Mice /
                      Mice, Inbred C57BL / Neoplasms: immunology / Neoplasms:
                      prevention $\&$ control / Oligodeoxyribonucleotides:
                      administration $\&$ dosage / Oligodeoxyribonucleotides:
                      pharmacology / Oligodeoxyribonucleotides: therapeutic use /
                      Poly I-C: administration $\&$ dosage / Poly I-C:
                      pharmacology / Poly I-C: therapeutic use / RAW 264.7 Cells /
                      Toll-Like Receptor 3: immunology / Toll-Like Receptor 9:
                      immunology / Adjuvants, Immunologic (NLM Chemicals) /
                      CPG-oligonucleotide (NLM Chemicals) / Cancer Vaccines (NLM
                      Chemicals) / Interleukin-6 (NLM Chemicals) / Liposomes (NLM
                      Chemicals) / Oligodeoxyribonucleotides (NLM Chemicals) /
                      Toll-Like Receptor 3 (NLM Chemicals) / Toll-Like Receptor 9
                      (NLM Chemicals) / Interferons (NLM Chemicals) / Poly I-C
                      (NLM Chemicals)},
      cin          = {Dresden common},
      ddc          = {610},
      cid          = {I:(DE-2719)6000013},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28069554},
      doi          = {10.1016/j.jconrel.2017.01.004},
      url          = {https://pub.dzne.de/record/139134},
}