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Adenovirus-mediated gene therapy of ovarian cancer in a mouse model
K Behbakht1, I Benjamin, H C Chiu
1Division of Gynecologic Oncology, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Objective:
Our purpose was to test the feasibility of adenovirus-mediated gene therapy of ovarian cancer.
Study Design:
Ovarian cancer cell lines were exposed to an adenovirus vector expressing a reporter gene (lacZ) and to the same vector bearing the herpes simplex virus thymidine kinase gene (Ad.RSVtk) followed by ganciclovir. lacZ expression and growth inhibition were quantitated. Immunodeficient mice were injected intraperitoneally and subcutaneously with human ovarian cancer cells and treated with Ad.RSVtk and ganciclovir. Statistical analyses included one-way analysis of variance and t tests.
Results:
Staining for lacZ demonstrated viral transduction in vitro. After exposure to Ad.RSVtk all cell lines showed significant (p < 0.0001, analysis of variance) cytotoxicity to ganciclovir. Human ovarian tumor cells established subcutaneously or intraperitoneally in immunodeficient mice responded to therapy with Ad.RSVtk followed by ganciclovir. Treated mice had a 10- to 20-fold lower subcutaneous tumor burden than did control mice. Additionally, no intraperitoneal tumors were observed in treated mice.
Conclusions:
Ovarian cancer cells are readily transduced with recombinant adenovirus and become sensitive to ganciclovir after transduction with Ad.RSVtk. These data support the development of this method for human clinical trials.
Insights
Adenovirus gene therapy is feasible for ovarian cancer. This approach effectively reduced tumor burden in mice by making cancer cells sensitive to ganciclovir treatment.
Area of Science:
- Oncology
- Gene Therapy
- Virology
Background:
- Ovarian cancer remains a significant health challenge with limited effective treatments.
- Gene therapy offers a novel approach to target and eliminate cancer cells.
Purpose of the Study:
- To evaluate the feasibility of using adenovirus-mediated gene therapy for ovarian cancer.
- To assess the efficacy of a specific adenovirus vector (Ad.RSVtk) in combination with ganciclovir against ovarian cancer cells.
Main Methods:
- Ovarian cancer cell lines were transduced with an adenovirus vector expressing the herpes simplex virus thymidine kinase gene (Ad.RSVtk).
- Transduced cells were treated with ganciclovir, and cytotoxicity was measured.
- The therapy was tested in immunodeficient mice bearing human ovarian cancer xenografts.
Main Results:
- Adenovirus-mediated gene transfer (lacZ reporter gene) was confirmed in vitro.
- Ovarian cancer cells transduced with Ad.RSVtk exhibited significant sensitivity to ganciclovir, leading to cell death.
- Mice treated with Ad.RSVtk and ganciclovir showed a substantial reduction in subcutaneous tumor growth (10-20 fold) and complete elimination of intraperitoneal tumors.
Conclusions:
- Recombinant adenovirus can efficiently transduce ovarian cancer cells.
- Transduction renders ovarian cancer cells susceptible to ganciclovir-induced cell death.
- This adenovirus-based gene therapy strategy shows promise for clinical development in ovarian cancer treatment.