Related Experiment Video
Updated: Aug 16, 2026
In vitro Mesothelial Clearance Assay that Models the Early Steps of Ovarian Cancer Metastasis
Published on: February 17, 2012
Replication of an integrin targeted conditionally replicating adenovirus on primary ovarian cancer spheroids
John T Lam1, Gerd J Bauerschmitz, Anna Kanerva
1Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Abstract:
Replication competent viruses hold promise for treatment of advanced cancers resistant to available therapeutic modalities. Although preliminary clinical results have substantiated their efficacy, preclinical development of these novel approaches is limited by assay substrates. The evaluation of candidate agents could be confounded by differences between primary tumor cells and tumor cell lines, as discordance in the levels of surface receptors relevant for viral entry has been reported. Since primary tumor cells are difficult to analyze ex vivo for longitudinal observation of virus replication, we developed three-dimensional aggregates or spheroids of unpassaged and purified ovarian cancer cells as a means for prolonging primary tumor cell viability and as a three-dimensional in vitro model for replicative viral infection. Ovarian cancer cells purified from ascites samples were sustained for 30 days while retaining the infection profile with tropism modified and unmodified adenoviruses (Ads). Cell line and primary cell spheroids were used to quantitate the replication and oncolytic potency of replicative Ads in preclinical testing for human ovarian cancer trials. Therefore, spheroids provide a method to sustain purified unpassaged primary ovarian cancer cells for extended periods and to allow evaluation of replicative viruses in a three-dimensional model.
Insights
Three-dimensional ovarian cancer spheroids prolong primary cell viability for improved preclinical testing of replication-competent viruses. This novel model enhances the evaluation of oncolytic adenoviruses (Ads) for advanced cancer treatment.
Area of Science:
- Oncolytic virology
- Cancer research
- 3D cell culture models
Background:
- Replication-competent viruses show promise for treating resistant cancers.
- Preclinical models often use cell lines, which may not accurately reflect primary tumor characteristics.
- Differences in surface receptors between primary cells and cell lines can affect viral entry and efficacy.
Purpose of the Study:
- To develop a novel 3D in vitro model using primary ovarian cancer cells for evaluating oncolytic viruses.
- To sustain unpassaged primary ovarian cancer cells ex vivo for extended periods.
- To assess the replication and oncolytic potency of adenoviruses (Ads) in a relevant tumor microenvironment.
Main Methods:
- Purified primary ovarian cancer cells from ascites were cultured as three-dimensional spheroids.
- Spheroids were maintained for up to 30 days.
- Infection profiles and replication of modified and unmodified adenoviruses (Ads) were analyzed in primary cell and cell line spheroids.
Main Results:
- Primary ovarian cancer cells in spheroids remained viable for 30 days.
- Spheroids retained infection profiles with adenoviruses (Ads).
- Replication and oncolytic potency of Ads were successfully quantified in the 3D spheroid model.
Conclusions:
- Three-dimensional ovarian cancer spheroids provide a method to sustain primary tumor cells ex vivo.
- This model allows for extended evaluation of replication-competent viruses in a 3D context.
- The spheroid model is valuable for preclinical testing of oncolytic adenoviruses (Ads) for ovarian cancer.
