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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
1998-2-4
|
| pubmed:abstractText |
Two human squamous cell carcinoma of the head and neck (SCCHN) cell lines, PCI-13 and PCI-52, were transduced with the retroviral construct containing human interleukin-2 (IL-2) cDNA and selected for neomycin resistance in G418 medium. Stably transduced SCCHN cells produced and secreted IL-2, which was shown to have biologic activity in a bioassay, using an IL-2-dependent CTLL-2 cell line. By immunohistochemistry, IL-2 gene-transduced PCI-13 cells were strongly positive for IL-2, and by flow cytometry showed both cell surface and intracytoplasmic expression of IL-2 protein. Expression of IL-2 mRNA was measured by quantitative RT-PCR and found to be considerably increased in transduced SCCHN relative to that in parental cells. There was no difference in expression of IL-2R between the parental and IL-2 gene-transduced cells. In vitro proliferation of IL-2 gene-transduced tumor cells was consistently more rapid than that of parental cells. Sensitivity of the parental and IL-2 gene-transduced targets to lysis or apoptosis mediated by purified human natural killer (NK) cells or IL-2-activated NK (A-NK) cells was comparable as measured in 4-hour 51Cr-release and 1-hour [3H]thymidine-release assays, respectively. However, transduced cells were significantly more sensitive than parental cells to these effectors in 24-hour MTT assays, most likely due to IL-2 production by the transduced targets. PCI-52 cells selected for in vivo experiments formed large subcutaneous tumors in immunosuppressed nude mice. Tumors established by subcutaneous injections of 1 x 10(7) IL-2 gene-transduced cells regressed completely by day 25, while those formed by parental or LacZ gene-transduced tumor cells grew progressively. Tumor regression was mediated by numerous mononuclear cells, identified as murine NK cells and macrophages by immunohistochemistry, which accumulated around the IL-2-secreting, but not parental, tumors within 5-6 days after tumor cell injections. Thus, IL-2 gene-transduced SCCHN cells produce functional IL-2 in vivo in amounts sufficient to support the recruitment to the tumor site and antitumor activity of cytotoxic effector cells. IL-2-secreting SCCHN cells may be a useful component of vaccines designed to induce and sustain effector cell activation at the tumor site.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0929-1903
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
4
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
366-76
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:9408607-Animals,
pubmed-meshheading:9408607-Carcinoma, Squamous Cell,
pubmed-meshheading:9408607-Cell Division,
pubmed-meshheading:9408607-Cell Line,
pubmed-meshheading:9408607-Cytotoxicity, Immunologic,
pubmed-meshheading:9408607-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:9408607-Head and Neck Neoplasms,
pubmed-meshheading:9408607-Humans,
pubmed-meshheading:9408607-Interleukin-2,
pubmed-meshheading:9408607-Interleukins,
pubmed-meshheading:9408607-Killer Cells, Natural,
pubmed-meshheading:9408607-Kinetics,
pubmed-meshheading:9408607-Mice,
pubmed-meshheading:9408607-Mice, Nude,
pubmed-meshheading:9408607-RNA, Messenger,
pubmed-meshheading:9408607-Recombinant Proteins,
pubmed-meshheading:9408607-Transcription, Genetic,
pubmed-meshheading:9408607-Transfection,
pubmed-meshheading:9408607-Transforming Growth Factor beta,
pubmed-meshheading:9408607-Transplantation, Heterologous,
pubmed-meshheading:9408607-Tumor Cells, Cultured,
pubmed-meshheading:9408607-Tumor Necrosis Factor-alpha
|
| pubmed:articleTitle |
In vitro and in vivo characteristics of human squamous cell carcinoma of the head and neck cells engineered to secrete interleukin-2.
|
| pubmed:affiliation |
Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania, USA.
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| pubmed:publicationType |
Journal Article
|