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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-7-27
pubmed:abstractText
The bacterial protein flagellin can trigger immune responses to infections by interacting with TLR5 on APCs, and Ag-flagellin fusion proteins can act as effective vaccines. We report that flagellin-related peptides containing a His-tag and sequence related to conserved N-motif (aa 85-111) of FliC flagellin, purportedly involved in the interaction of flagellin with TLR5, can be used to target delivery of liposomal Ag to APCs in vitro and in vivo. When engrafted onto liposomes, two flagellin-related peptides, denoted as 9Flg and 42Flg, promoted strong liposome binding to murine bone marrow-derived dendritic cells and CD11c(+) splenocytes, and cell binding correlated with expression of TLR5. Liposomes engrafted with 9Flg or 42Flg induced functional MyD88-dependent maturation of dendritic cells in vivo. The vaccination of mice with 9Flg liposomes containing OVA induced OVA-specific T cell priming, increased the number of Ag-responsive IFN-gamma-producing CD8(+) T cells, and increased Ag-specific IgG(1) and IgG(2b) in serum. Importantly, the vaccination of C57BL/6 mice with syngeneic B16-OVA-derived plasma membrane vesicles, engrafted with 9Flg or 42Flg, potently inhibited tumor growth/metastasis and induced complete tumor regression in the majority of mice challenged with the syngeneic B16-OVA melanoma, in the lung and s.c. tumor models. Strong antitumor responses were also seen in studies using the s.c. P815 tumor model. Therefore, vaccination with Ag-containing liposomes engrafted with 9Flg or 42Flg is a powerful strategy to exploit the innate and adaptive immune systems for the development of potent vaccines and cancer immunotherapies.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
185
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1744-54
pubmed:dateRevised
2011-3-25
pubmed:meshHeading
pubmed-meshheading:20610649-Amines, pubmed-meshheading:20610649-Amino Acid Sequence, pubmed-meshheading:20610649-Animals, pubmed-meshheading:20610649-Antigens, Neoplasm, pubmed-meshheading:20610649-CHO Cells, pubmed-meshheading:20610649-Cancer Vaccines, pubmed-meshheading:20610649-Cell Line, pubmed-meshheading:20610649-Cell Line, Tumor, pubmed-meshheading:20610649-Conserved Sequence, pubmed-meshheading:20610649-Cricetinae, pubmed-meshheading:20610649-Cricetulus, pubmed-meshheading:20610649-Drug Delivery Systems, pubmed-meshheading:20610649-Flagellin, pubmed-meshheading:20610649-Hep G2 Cells, pubmed-meshheading:20610649-Humans, pubmed-meshheading:20610649-Liposomes, pubmed-meshheading:20610649-Mastocytoma, pubmed-meshheading:20610649-Melanoma, Experimental, pubmed-meshheading:20610649-Mice, pubmed-meshheading:20610649-Mice, Inbred C57BL, pubmed-meshheading:20610649-Mice, Inbred DBA, pubmed-meshheading:20610649-Molecular Sequence Data, pubmed-meshheading:20610649-Nitrilotriacetic Acid, pubmed-meshheading:20610649-Peptides
pubmed:year
2010
pubmed:articleTitle
Antigen-containing liposomes engrafted with flagellin-related peptides are effective vaccines that can induce potent antitumor immunity and immunotherapeutic effect.
pubmed:affiliation
Division of Biomedical Science and Biochemistry, Research School of Biology, College of Medicine, Biology and Environment, Australian National University, Canberra, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't