Linked Life Data

16415100

Source:http://linkedlifedata.com/resource/pubmed/id/16415100

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-2-27
pubmed:abstractText
We have evaluated the capacity of a novel, nanoparticle-based tumor vaccine to eradicate established tumors in mice. C57BL/6 mice were intradermally (i.d.) inoculated with ovalbumin (OVA)-expressing EG-7 tumor cells. When the tumor size reached 7-8 mm, the tumor-bearing mice were i.d. injected near the tumor-draining lymph node (DLN) with liposomes encapsulated with unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotides (CpG-ODN) (CpG-liposomes) co-encapsulated with OVA. This vaccination protocol markedly prevented the growth of the established tumor mass and approximately 50% of tumor-bearing mice became completely cured. Tumor eradication correlated with the generation of OVA/H-2K(b)-tetramer(+) CTLs in the tumor DLN and at the tumor site with specific cytotoxicity toward EG-7 cells. Interestingly, tetramer(+) CTLs failed to be induced in lymph node-deficient Aly/Aly mice. Thus, tetramer(+) CTLs appeared to be generated in the tumor DLN and subsequently migrated into the tumor site. In vivo antibody blocking experiments revealed that CD8(+) T cells, but not CD4(+) T, NK or NKT cells, were the major effector cells mediating tumor eradication. CTL induction was also inhibited when vaccinated tumor-bearing mice were treated with both anti-IFN-alpha and anti-IFN-beta mAbs but not with anti-IFN-alpha or anti-IFN-beta mAb alone. Neither IFN-gamma(-/-) nor IL-12(-/-) mice showed impaired induction of tetramer(+) CTLs. Thus, these findings revealed that CpG-ODN-induced IFN-alpha/beta, but not IL-12 or IFN-gamma, is critical for the generation of tumor-specific CTLs in response to vaccination. These results highlight the potential utility of CpG-liposomes co-encapsulated with protein tumor antigens as therapeutic vaccines in cancer patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0953-8178
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
425-34
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16415100-Adjuvants, Immunologic, pubmed-meshheading:16415100-Animals, pubmed-meshheading:16415100-Antigens, Neoplasm, pubmed-meshheading:16415100-Cancer Vaccines, pubmed-meshheading:16415100-Female, pubmed-meshheading:16415100-Humans, pubmed-meshheading:16415100-Interferon Type I, pubmed-meshheading:16415100-Interferon-gamma, pubmed-meshheading:16415100-Interleukin-12, pubmed-meshheading:16415100-Liposomes, pubmed-meshheading:16415100-Lymph Nodes, pubmed-meshheading:16415100-Mice, pubmed-meshheading:16415100-Mice, Inbred C57BL, pubmed-meshheading:16415100-Models, Immunological, pubmed-meshheading:16415100-Neoplasms, Experimental, pubmed-meshheading:16415100-Oligodeoxyribonucleotides, pubmed-meshheading:16415100-Ovalbumin, pubmed-meshheading:16415100-T-Lymphocytes, Cytotoxic, pubmed-meshheading:16415100-Th1 Cells
pubmed:year
2006
pubmed:articleTitle
An indispensable role of type-1 IFNs for inducing CTL-mediated complete eradication of established tumor tissue by CpG-liposome co-encapsulated with model tumor antigen.
pubmed:affiliation
Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't