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
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.