|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
11
|
|
pubmed:dateCreated |
2005-5-20
|
|
pubmed:abstractText |
We previously demonstrated that IL-4 gene-transfected glioma cell vaccines induce effective therapeutic immunity in preclinical glioma models, and have initiated phase I trials of these vaccines in patients with malignant gliomas. To gain additional mechanistic insight into the efficacy of this approach, we have treated mice bearing the MCA205 (H-2(b)) or CMS-4 (H-2(d)) sarcomas. IL-12/23 p40(-/-) and IFN-gamma(-/-) mice, which were able to reject the initial inoculation of IL-4 expressing tumors, failed to mount a sustained systemic response against parental (nontransfected) tumor cells. Paracrine production of IL-4 in vaccine sites promoted the accumulation and maturation of IL-12p70-secreting tumor-infiltrating dendritic cells (TIDCs). Adoptive transfer of TIDCs isolated from vaccinated wild-type, but not IL-12/23 p40(-/-), mice were capable of promoting tumor-specific CTL responses in syngeneic recipient animals. Interestingly, both STAT4(-/-) and STAT6(-/-) mice failed to reject IL-4-transfected tumors in concert with the reduced capacity of TIDCs to produce IL-12p70 and to promote specific antitumor CTL reactivity. These results suggest that vaccines consisting of tumor cells engineered to produce the type 2 cytokine, IL-4, critically depend on type 1 immunity for their observed therapeutic efficacy.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12 Subunit p40,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/STAT4 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT6 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stat6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jun
|
|
pubmed:issn |
0022-1767
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
174
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
7194-201
|
|
pubmed:dateRevised |
2008-11-21
|
|
pubmed:meshHeading |
pubmed-meshheading:15905564-Animals,
pubmed-meshheading:15905564-Cancer Vaccines,
pubmed-meshheading:15905564-Cell Line, Tumor,
pubmed-meshheading:15905564-Cell Movement,
pubmed-meshheading:15905564-DNA-Binding Proteins,
pubmed-meshheading:15905564-Dendritic Cells,
pubmed-meshheading:15905564-Female,
pubmed-meshheading:15905564-Fibrosarcoma,
pubmed-meshheading:15905564-Graft Rejection,
pubmed-meshheading:15905564-Immunity, Cellular,
pubmed-meshheading:15905564-Interferon-gamma,
pubmed-meshheading:15905564-Interleukin-12,
pubmed-meshheading:15905564-Interleukin-12 Subunit p40,
pubmed-meshheading:15905564-Interleukin-4,
pubmed-meshheading:15905564-Killer Cells, Natural,
pubmed-meshheading:15905564-Mice,
pubmed-meshheading:15905564-Mice, Inbred BALB C,
pubmed-meshheading:15905564-Mice, Inbred C57BL,
pubmed-meshheading:15905564-Mice, Knockout,
pubmed-meshheading:15905564-Mice, Nude,
pubmed-meshheading:15905564-Protein Subunits,
pubmed-meshheading:15905564-STAT4 Transcription Factor,
pubmed-meshheading:15905564-STAT6 Transcription Factor,
pubmed-meshheading:15905564-Sarcoma, Experimental,
pubmed-meshheading:15905564-T-Lymphocyte Subsets,
pubmed-meshheading:15905564-Trans-Activators,
pubmed-meshheading:15905564-Transfection
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
IL-4-transfected tumor cell vaccines activate tumor-infiltrating dendritic cells and promote type-1 immunity.
|
|
pubmed:affiliation |
Department of Neurological Surgery, University of Pittsburgh School of Medicine, PA 15213, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
