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CD40 Is Expressed on Ovarian Cancer Cells and Can Be Utilized for Targeting Adenoviruses¹

Department of Biotechnology and Molecular Medicine, A. I.Virtanen Institute for Molecular Sciences, University of Kuopio, 70211 Kuopio, Finland [T. H., J. W.], and Division of Human Gene Therapy, Departments of Medicine, Pathology, and Surgery and the Gene Therapy Center [T. H., A. H., A. V. P., S. D. B., A. K., D. T. C.], Department of Biomedical Engineering [A. H.], and Division of Hematology-Oncology [C. K. A., T. V. S.], University of Alabama at Birmingham, Birmingham, Alabama 35294-3300

Purpose: CD40, a member of the tumor necrosis factor receptor superfamily, is widely expressed on various cell types in addition to hematopoietic cells. Recent studies show that CD40 expression is related to several carcinomas, although its role in cancer pathobiology is unknown. In this study, we demonstrate the expression of CD40 on several ovarian carcinoma cell lines and the ability of CD40 to mediate targeted adenoviral infection in vitro.

Experimental Design: CD40 expression on ovarian cancer cell lines and clinical patient samples was examined by reverse transcription-PCR and flow cytometry. To study the utilization of CD40 for gene delivery, we precomplexed a luciferase coding adenovirus (Ad), Ad5luc1, with a CD40-targeting molecule (CAR/G28).

Results: According to our studies, all of the examined ovarian cancer cell lines are expressing CD40. In addition, mRNA for CD40 was detected in every primary tumor sample, suggesting that CD40 is also expressed in vivo. Compared with nontargeted Ad, gene transfer was increased up to 40-fold in CD40+ cells when CD40-targeted Ad was used. Supporting the relation of targeted system to CD40, increasing the amount of targeting fusion protein results in dose response. Furthermore, blockade of CD40 receptors on cell surface decreases the infectability of CD40+ cells with CD40-targeted virus, indicating the specificity of the targeting system for CD40.

Conclusions: These results suggest that CD40 is present in ovarian cancer cells and can be used for targeted gene delivery in a CAR-independent manner, circumventing the problem of the low expression levels of CAR in various cancer cells.

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