Back to Search
Start Over
Treatment of disseminated ovarian cancer using nonviral interleukin-12 gene therapy delivered intraperitoneally.
- Source :
-
The journal of gene medicine [J Gene Med] 2009 Aug; Vol. 11 (8), pp. 718-28. - Publication Year :
- 2009
-
Abstract
- Background: The poor prognosis associated with ovarian cancer is primarily the result of delayed diagnosis and the lack of an effective treatment for advanced disease. Use of novel immunotherapy strategies are being evaluated that work to enhance local and systemic immune responses against cancer cells and can possibly work together with traditional cytotoxic chemotherapy regimens to produce more effective treatment options.<br />Methods: In the present study, we describe a gene-based therapy whereby the anticancer cytokine interleukin-12 gene (pmIL-12) is formulated with a synthetic polymeric delivery vehicle (PPC) and administered intraperitoneally into a mouse model of disseminated ovarian cancer.<br />Results: The administration of pmIL-12/PPC in tumor-bearing mice was associated with a shift towards a Th1 immune state, including significant increases in murine IL-12 (mIL-12) and interferon (IFN)-gamma (mIFN-gamma) in ascites fluid, with little change in systemic levels of these proteins. The mIL-12 protein was detectable for several days and could be reintroduced with subsequent injections. We show that treatment delayed the onset of ascites formation and improved survival in a dose-dependent manner. A significant decrease in vascular endothelial growth factor was associated with pmIL-12/PPC delivery and believed to play a predominant role in inhibiting ascites accumulation. Administration of pmIL-12/PPC was associated with minimal toxicity and, when combined with standard chemotherapies, resulted in additive improvement in survival.<br />Conclusions: Taken together, these results suggest that pmIL-12/PPC may be an effective strategy for inhibiting progression of disseminated ovarian cancer and may offer a new option for treatment of advanced disease that can be used to complement standard therapies.
- Subjects :
- Animals
Ascites metabolism
Blood Cell Count
Body Weight drug effects
Carboplatin pharmacology
Carboplatin therapeutic use
Female
Gene Expression Regulation, Neoplastic drug effects
Injections, Intraperitoneal
Interleukin-12 administration & dosage
Interleukin-12 metabolism
Mice
Mice, Inbred C57BL
Neoplasm Proteins blood
Ovarian Neoplasms blood
Ovarian Neoplasms drug therapy
Paclitaxel pharmacology
Paclitaxel therapeutic use
RNA, Messenger genetics
RNA, Messenger metabolism
Survival Analysis
Tumor Burden drug effects
Viruses
Genetic Therapy
Interleukin-12 genetics
Interleukin-12 therapeutic use
Ovarian Neoplasms genetics
Ovarian Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1521-2254
- Volume :
- 11
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The journal of gene medicine
- Publication Type :
- Academic Journal
- Accession number :
- 19507172
- Full Text :
- https://doi.org/10.1002/jgm.1356