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PredicateObject
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
pubmed:status
MEDLINE
pubmed:issn
0929-1903
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
175-85
pubmed:dateRevised
2006-5-1
pubmed:meshHeading
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