Intravesical liposome-mediated interleukin-2 gene therapy in orthotopic murine bladder cancer model Journal Article
| Authors: | Horiguchi, Y.; Larchian, W. A.; Kaplinsky, R.; Fair, W. R.; Heston, W. D. W. |
| Article Title: | Intravesical liposome-mediated interleukin-2 gene therapy in orthotopic murine bladder cancer model |
| Abstract: | Using a novel orthotopic MBT-2 murine bladder tumor model, we evaluated the feasibility of intravesical gene therapy utilizing a cationic liposome, DMRIE/DOPE. Superficial bladder tumors were consistently established by intravesical 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-gal) gene expression was preferentially evident in bladder tumors and was present for at least 7 days after a single 30 min in situ transfection. Murine interleukin-2 (IL-2) gene was used for treatment of 3-day-old pre-established bladder tumors. Forty percent of animals treated with IL-2 gene were completely free of tumors by 60 days following the initial tumor implantation, while all control groups treated with beta-gal gene died. Those animals initially cured of pre-established tumors were completely resistant to a subsequent tumor re-challenge and their splenocyte-derived cytotoxic T lymphocytes were shown to be specific to MBT-2 cells, indicating that immunological memory against MBT-2 tumors was elicited by the treatment. These results demonstrate the possibility of an effective clinical application of this in situ intravesical IL-2 gene delivery system to high-risk superficial bladder tumors, obviating a need for tumor procurement and ex vivo gene transfer. |
| Keywords: | bladder cancer; immunotherapy; gene therapy; in-vivo; intravesical; liposome; interleukin-2; plasmid dna; cells; bacillus-calmette-guerin; immune-response; antitumor; vectors; tumor-bearing mice; antimetastatic vaccination |
| Journal Title: | Gene Therapy |
| Volume: | 7 |
| Issue: | 10 |
| ISSN: | 0969-7128 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2000-05-01 |
| Start Page: | 844 |
| End Page: | 851 |
| Language: | English |
| ACCESSION: | WOS:000087004700006 |
| DOI: | 10.1038/sj.gt.3301157 |
| PROVIDER: | wos |
| PUBMED: | 10845722 |
| Notes: | Article -- Source: Wos |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work