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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
1996-12-27
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pubmed:abstractText |
Gene-transfected tumour cells were used to cure mice bearing lung metastases by the parental, non-transduced mammary adenocarcinoma (TSA-pc). Repeated subcutaneous (s.c.) administrations of mitomycin C (MitC)-treated interferon gamma (IFN-gamma) transfectants induced a 90% inhibition in the number of lung metastases. Therapeutic effect required an intact T-cell response, as shown by the lack of efficacy in nude mice. Autocrine stimulation by IFN-gamma induces specific modifications in the phenotype of transfectants that acquire a high metastatic ability and show a high expression of IFN-responsive genes; these two features were exploited to design two experimental protocols to obtain an improvement of the therapeutic effect. The increased metastatic ability of IFN-gamma transfectants was used to deliver IFN-gamma selectively to the lungs of mice bearing TSA-pc pulmonary metastases. A significant therapeutic effect was obtained when TSA-pc experimental metastases were treated by repeated intravenous (i.v.) injections of MitC IFN-gamma transfectants. Since i.v. administrations of IFN-gamma transfectants did not induce immune memory, the therapeutical effect appeared to depend on the inflammatory-like response activated by local IFN release. To exploit the autocrine stimulation of IFN-sensitive genes an IFN-gamma transfectant clone was subjected to a second transfection with an allogeneic class I MHC gene (H-2K(b) or H-2D(h)). IFN-gamma plus MHC double transfectants maintained IFN-gamma release, showed a very high expression of the MHC gene products, stimulated both macrophages and T cells, and were less tumorigenic in immunocompetent mice than the parent IFN-gamma clone. Therapeutic efficacy of double transfectant IFN-gamma plus H-2D(b) cells against TSA-pc was superior to single transfectants, showing that the reaction elicited by genetically engineered cells can be selectively tuned to increase therapeutic efficacy.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-1516042,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-1588273,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-1900037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-1906055,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-1906780,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-2123742,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-2512580,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-3223398,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-3464979,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-7548274,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-7906727,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-7927928,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-7954438,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-8097319,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-8137291,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-8155261,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-8173240,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-8326126,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-8340258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-8370628,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-8432988,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-8459207,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-8464888,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8932336-8569177
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0007-0920
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
74
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1564-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8932336-Adenocarcinoma,
pubmed-meshheading:8932336-Animals,
pubmed-meshheading:8932336-Female,
pubmed-meshheading:8932336-Gene Therapy,
pubmed-meshheading:8932336-Interferon-gamma,
pubmed-meshheading:8932336-Lung Neoplasms,
pubmed-meshheading:8932336-Major Histocompatibility Complex,
pubmed-meshheading:8932336-Mammary Neoplasms, Experimental,
pubmed-meshheading:8932336-Mice,
pubmed-meshheading:8932336-Mice, Inbred BALB C,
pubmed-meshheading:8932336-Transduction, Genetic,
pubmed-meshheading:8932336-Transfection
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pubmed:year |
1996
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pubmed:articleTitle |
Therapy of murine mammary carcinoma metastasis with interferon gamma and MHC gene-transduced tumour cells.
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pubmed:affiliation |
Istituto di Cancerologia, Universita di Bologna, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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