Linked Life Data

18202769

Source:http://linkedlifedata.com/resource/pubmed/id/18202769

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pubmed-article:18202769pubmed:abstractTextCancer immunotherapy using dendritic cells (DCs) adenovirally transduced with the whole tumor-associated antigen (TAA) gene is an effective approach. Streptococcal preparation OK-432 is useful for stimulating DCs in terms of maturation. In this study, we established carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocytes (CTLs) using in vitro stimulation with adenovirally modified human DCs that express CEA. We investigated whether OK-432 stimulation could be more effective in inducing CEA-specific CTLs compared with other typical stimuli. DCs adenovirally transduced with the CEA gene were cultured under various conditions with tumor necrosis factor (TNF)-alpha, lipopolysaccharide (LPS), or OK-432. A cytotoxicity assay using peripheral blood mononuclear cell (PBMC)-derived CTLs was performed in a 4 h-51Cr release assay. OK-432 stimulated immature DCs to acquire a mature phenotype and to produce significant amounts of T-helper 1 cytokines. In all groups (immature DCs, TNF-alpha/DCs, LPS/DCs, OK-432/DCs), CEA-specific CTLs were generated. OK-432-stimulated DCs (HLA-A24) induced the most potent cytotoxic activity against CEA-expressing targets (A24) but not against controls. OK-432/DCs were able to induce markedly potent CTLs specific to target cells pulsed with CEA652 peptide (HLA-A24-restricted peptide), although others failed to induce potent CTLs. In conclusion, the CTL induction protocol using adenovirally modified DCs that express CEA after maturation with OK-432 showed a potent antitumor activity against CEA-expressing target cells, and is therefore promising for clinical applications as a cancer vaccine therapy.lld:pubmed
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pubmed-article:18202769pubmed:authorpubmed-author:YamaueHirokiHlld:pubmed
pubmed-article:18202769pubmed:authorpubmed-author:MatsudaKenjiKlld:pubmed
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pubmed-article:18202769pubmed:authorpubmed-author:NakamuraMasak...lld:pubmed
pubmed-article:18202769pubmed:authorpubmed-author:NakamoriMikih...lld:pubmed
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pubmed-article:18202769pubmed:authorpubmed-author:OjimaToshiyas...lld:pubmed
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pubmed-article:18202769pubmed:pagination459-66lld:pubmed
pubmed-article:18202769pubmed:dateRevised2008-11-21lld:pubmed
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pubmed-article:18202769pubmed:articleTitleStreptococcal preparation OK-432 promotes the capacity of dendritic cells (DCs) to prime carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocyte responses induced with genetically modified DCs that express CEA.lld:pubmed
pubmed-article:18202769pubmed:affiliationSecond Department of Surgery, Wakayama Medical University, School of Medicine, 811-1 Kimidera, Wakayama 641-8510, Japan.lld:pubmed
pubmed-article:18202769pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:18202769pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed