Linked Life Data

16645618

Source:http://linkedlifedata.com/resource/pubmed/id/16645618

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2006-7-19
pubmed:abstractText
Although CD4(+) Type-1T helper (Th1) cells secreting interferon-gamma (IFN-gamma) appear to play an essential role in promoting durable antitumor immunity, we have previously shown that patients with cancer exhibit dysfunctional Th1-type responses against epitopes derived from tumor antigens, such as MAGE-A6. Here, we engineered human dendritic cells (DCs) to secrete high levels of the IFN-gamma-inducing cytokines, interleukin (IL)-12p70 and IL-18, via recombinant adenoviral infection to generate an in vitro stimulus capable of promoting previously deficient patient Th1-type responses. Dendritic cells co-infected with Ad.IL-12 and Ad.IL-18 (DC.IL-12/18) were more effective at stimulating MAGE-A6-specific Th1-type CD4(+) T-cell responses than DCs infected with either of the cytokine vectors alone, control Ad.Psi5 virus or uninfected DCs. Furthermore, we show that DC.IL-12/18 loaded with recombinant MAGE-A6 protein (rMAGE) and used as in vitro stimulators promote Th1-type immunity that is frequently directed against multiple MAGE-A6-derived epitopes. The superiority of DC.IL-12/18-based stimulations in melanoma patients was independent of disease stage or current disease status. Based on these results, we believe this modality may prove clinically useful as a vaccine platform to promote the recovery of tumor antigen-specific, Th1-type CD4(+) T-cell responses in patients with cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0929-1903
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
798-805
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
IL-12p70 and IL-18 gene-modified dendritic cells loaded with tumor antigen-derived peptides or recombinant protein effectively stimulate specific Type-1 CD4+ T-cell responses from normal donors and melanoma patients in vitro.
pubmed:affiliation
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, N.I.H., Extramural