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Updated: Aug 8, 2026
In vitro Mesothelial Clearance Assay that Models the Early Steps of Ovarian Cancer Metastasis
Published on: February 17, 2012
Mesothelin-mediated targeting of adenoviral vectors for ovarian cancer gene therapy
M Breidenbach1, D T Rein, M Everts
1Division of Human Gene Therapy, Departments of Medicine, Surgery, Pathology and the Gene Therapy Center, Birmingham, AL 35294-2172, USA.
Abstract:
Adenoviruses (Ads) are efficient gene transfer vehicles, but Ad-mediated gene therapy for ovarian cancer remains limited in vivo by inefficient and nonspecific gene transfer. Mesothelin (MSLN), a cell surface glycoprotein, is overexpressed in ovarian cancer but not in normal tissues except mesothelial cells. Therefore, MSLN is an attractive candidate for transcriptional and transductional targeting in the context of ovarian cancer gene therapy. We evaluated the expression of MSLN mRNA and MSLN surface protein in ovarian cancer cells. Ads containing the MSLN promoter driving reporter gene expression were created and tested in ovarian cancer cell lines and purified ovarian cancer cells isolated from patients. To evaluate transductional targeting, we used an Ad vector containing an Fc-binding domain within the fiber protein, which served as a docking domain for binding with anti-MSLN immunoglobulins. Both RT-PCR and flow cytometry revealed high MSLN gene and protein expression in ovarian cancer cells. The MSLN promoter was activated in ovarian cancer cells, but showed significantly reduced activity in normal control cells. Transductional targeting of Ads via anti-MSLN antibody increased transgene expression in ovarian cancer cells. This report describes the use of MSLN for transcriptional as well as transductional targeting strategies for ovarian cancer gene therapy.
Insights
Targeting ovarian cancer with adenoviruses (Ads) is improved by using mesothelin (MSLN) for gene therapy. MSLN enhances both transcriptional and transductional targeting of Ads in ovarian cancer cells.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Adenoviruses (Ads) are effective gene transfer vectors, but their use in ovarian cancer gene therapy is hindered by inefficient and nonspecific gene delivery.
- Mesothelin (MSLN), a cell surface glycoprotein, is highly expressed in ovarian cancer, making it a promising target for selective cancer therapy.
Purpose of the Study:
- To evaluate mesothelin (MSLN) as a target for both transcriptional and transductional strategies in adenovirus-mediated ovarian cancer gene therapy.
- To assess the feasibility of using the MSLN promoter for transcriptional targeting and anti-MSLN antibodies for transductional targeting of adenoviruses in ovarian cancer.
Main Methods:
- Adenovirus vectors were engineered with the MSLN promoter to drive reporter gene expression.
- MSLN mRNA and protein expression were analyzed in ovarian cancer cells using RT-PCR and flow cytometry.
- Adenovirus vectors were modified with an Fc-binding domain for antibody-mediated targeting to MSLN on ovarian cancer cells.
Main Results:
- Ovarian cancer cells demonstrated high expression of MSLN mRNA and surface protein.
- The MSLN promoter showed significant activity in ovarian cancer cells but minimal activity in normal control cells.
- Targeting adenoviruses with anti-MSLN antibodies enhanced transgene expression in ovarian cancer cells.
Conclusions:
- Mesothelin (MSLN) is a viable target for developing targeted adenovirus-based gene therapies for ovarian cancer.
- Both transcriptional targeting via the MSLN promoter and transductional targeting using anti-MSLN antibodies show promise for improving ovarian cancer gene therapy efficacy and specificity.
