Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
|
pubmed:dateCreated |
1996-11-8
|
pubmed:abstractText |
The plasmid DNA vector pVCL-1102 containing the coding sequence for the human IL-2 gene was evaluated for expression in tumor cells in vitro and in vivo. In vitro transfection of murine B16 tumor cells with pVCL-1102 resulted in the expression of 36,000 IU (5.7 micrograms) of biologically active IL-2/10(6) cells/48 h. In vitro transfection of human tumor lines and primary cultures from human biopsies with pVCL-1102 resulted in the expression of 1,289 to 9345 IU of IL-2/10(6) cells/48 h and 30 to 794 IU of IL-2/10(6) cells/48 h, respectively. In vivo, direct intratumor injection of pVCL-1102 resulted in retention of intact plasmid DNA in the tumor tissue and IL-2 secretion by cell cultures derived from the injected tumors. Formulation of pVCL-1102 with the cationic lipid DMRIE/DOPE inhibited DNA degradation and enhanced in vivo transfection efficiency over plasmid DNA alone. Antitumor activity of the pVCL-1102/DMRIE/DOPE complex was evaluated in a B16 melanoma model in mice. An IL-2-specific effect could not be demonstrated in a subcutaneous model because the intratumor injection of plasmid DNA lacking the IL-2 coding sequence also resulted in a significant reduction in tumor volume. However, an IL-2-specific effect was observed when B16 cells were transfected in vitro prior to implantation into the mouse. Transient transfection of B16 cells with pVCL-1102 rendered the cells less tumorigenic in vivo and produced a significant reduction in tumor volume. These data demonstrate that a plasmid DNA expression vector can be used to deliver the IL-2 gene to tumor cells in vitro and in vivo, resulting in the expression of significant levels of IL-2 protein. These data also illustrate the need for the use of appropriate controls when evaluating the in vivo biological activity of plasmid DNA in murine tumor models.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Drug Carriers,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Liposomes
|
pubmed:status |
MEDLINE
|
pubmed:issn |
0929-1903
|
pubmed:author |
pubmed-author:AndersonDD,
pubmed-author:GromkowskiS HSH,
pubmed-author:HershEE,
pubmed-author:HobartPP,
pubmed-author:KhatibiSS,
pubmed-author:LatimerTT,
pubmed-author:LeuFF,
pubmed-author:ManthorpeMM,
pubmed-author:MargalithMM,
pubmed-author:MarquesLL,
pubmed-author:NormanJJ,
pubmed-author:ParkerS ESE,
pubmed-author:StopeckA TAT,
pubmed-author:YankauckasMM
|
pubmed:issnType |
Print
|
pubmed:volume |
3
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
175-85
|
pubmed:dateRevised |
2006-5-1
|
pubmed:meshHeading |
pubmed-meshheading:8725882-Animals,
pubmed-meshheading:8725882-Blotting, Southern,
pubmed-meshheading:8725882-Cell Line,
pubmed-meshheading:8725882-DNA,
pubmed-meshheading:8725882-DNA Primers,
pubmed-meshheading:8725882-Drug Carriers,
pubmed-meshheading:8725882-Gene Expression,
pubmed-meshheading:8725882-Gene Therapy,
pubmed-meshheading:8725882-Humans,
pubmed-meshheading:8725882-Interleukin-2,
pubmed-meshheading:8725882-Kinetics,
pubmed-meshheading:8725882-Liposomes,
pubmed-meshheading:8725882-Melanoma, Experimental,
pubmed-meshheading:8725882-Mice,
pubmed-meshheading:8725882-Mice, Inbred C57BL,
pubmed-meshheading:8725882-Plasmids,
pubmed-meshheading:8725882-Polymerase Chain Reaction,
pubmed-meshheading:8725882-Tumor Cells, Cultured
|
pubmed:articleTitle |
Plasmid DNA gene therapy: studies with the human interleukin-2 gene in tumor cells in vitro and in the murine B16 melanoma model in vivo.
|
pubmed:affiliation |
Vical, Inc., San Diego, CA 92121, USA.
|
pubmed:publicationType |
Journal Article
|