Intravesical liposome-mediated interleukin-2 gene therapy in orthotopic murine bladder cancer model

Citation
Y. Horiguchi et al., Intravesical liposome-mediated interleukin-2 gene therapy in orthotopic murine bladder cancer model, GENE THER, 7(10), 2000, pp. 844-851
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
GENE THERAPY
ISSN journal
0969-7128 → ACNP
Volume
7
Issue
10
Year of publication
2000
Pages
844 - 851
Database
ISI
SICI code
0969-7128(200005)7:10<844:ILIGTI>2.0.ZU;2-5
Abstract
Using a novel orthotopic MBT-2 murine bladder tumor model, we evaluated the feasibility of intravesical gene therapy utilizing a cationic liposome, DM RIE/DOPE. Superficial bladder tumors were consistently established by intra vesical instillation of 5 x 10(5) MBT-2 cells in syngeneic C3H female mice. In situ gene transfer to bladder tumors was accomplished via intravesical instillation of plasmid DNA/DMRIE/DOPE lipoplex. beta-Galactosidase (beta-g al) gene expression was preferentially evident in bladder tumors and was pr esent for at least 7 days after a single 30 min in situ transfection. Murin e interleukin-2 (IL-2) gene was used for treatment of 3-day-old pre-establi shed bladder tumors. Forty percent of animals treated with IL-2 gene were c ompletely free of tumors by 60 days following the initial tumor implantatio n, while all control groups treated with beta-gal gene died. Those animals initially cured of pre-established tumors were completely resistant to a su bsequent tumor re-challenge and their splenocyte-derived cytotoxic T lympho cytes were shown to be specific to MBT-2 cells, indicating that immunologic al memory against MBT-2 tumors was elicited by the treatment. These results demonstrate the possibility of an effective clinical application of this i n situ intravesical IL-2 gene delivery system to high-risk superficial blad der tumors, obviating a need for tumor procurement and ex vivo gene transfe r.