Linked Life Data

9826461

Source:http://linkedlifedata.com/resource/pubmed/id/9826461

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-1-4
pubmed:abstractText
The immunosuppressive protein transforming growth factor beta (TGF-beta) inhibits the activation of various immune effector cells including cytotoxic T lymphocytes and may therefore inhibit the efficacy of immunostimulatory interleukin-2 (IL-2) gene therapy. In this study, we investigated the effect of TGF-beta downregulation on IL-2 gene therapy in the intraperitoneal model of murine ovarian teratoma (MOT). MOT cells, like many human ovarian carcinomas, were found to produce TGF-beta. Production of TGF-beta by MOT cells was suppressed using a TGF-beta antisense plasmid vector (pCEP4/TGF-beta antisense). Subcutaneous immunization of C3H mice with a mixture of IL-2 gene-transduced fibroblasts and TGF-beta antisense-modified MOT cells induced significantly better protection against a subsequent intraperitoneal tumor challenge compared with immunization with unmodified MOT cells alone [11/16 (69%) vs 4/21 (19%) tumor-free animals, P < 0.01]. Immunization with either a mixture of IL-2 gene modified fibroblasts and unmodified MOT cells [2/12 (17%) tumor-free animals] or TGF-beta antisense-modified MOT cells alone (0/13 tumor free animals) failed to induce significant protection compared with immunization with unmodified MOT cells. These data show that combined TGF-beta antisense and IL-2 gene therapy is required to generate effective antitumor responses in the MOT model. Our findings suggest that tumor cell expression of immunosuppressive factors may inhibit cytokine immunogene therapy and may have potential implications for the development of future clinical immunogene therapy protocols.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0090-8258
pubmed:author
pubmed:copyrightInfo
Copyright 1998 Academic Press.
pubmed:issnType
Print
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
204-10
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Combination of transforming growth factor beta antisense and interleukin-2 gene therapy in the murine ovarian teratoma model.
pubmed:affiliation
Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, California, 90095-1740, USA. oliverdo@hotmail.com
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't