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Determination of molecules regulating gene delivery using adenoviral vectors in ovarian carcinomas

Gene Therapy volume 9, pages 1093–1100 (2002)Cite this article

Abstract

Gene therapeutic approaches currently favor adenoviral vectors over alternatively available vector systems. Ovarian cancer represents an attractive model for an intraperitoneal adenovirus-based gene therapy, which is now under intensive clinical investigation. Adenovirus-mediated gene transfer depends on adequate virus uptake and thus on the presence of sufficient amounts of high-affinity coxsackie-adenovirus receptor (CAR) and αvβ3- and αvβ5 integrins on target cells. This fact has been ignored in most ongoing clinical trials. This investigation, therefore, determined expression of CAR by immunohistochemistry in 37 ovarian carcinomas and compared it with that of αvβ3 and αvβ5 integrins. In all samples, except one undifferentiated carcinoma, CAR was immunohistochemically demonstrable. Grade 1 tumors exhibited stronger CAR immunostaining as compared with higher-grade cancers (P < 0.03). Integrins αvβ3 and αvβ5 were detectable in 62% and 65% of carcinomas, respectively, and staining for both classes correlated positively (P < 0.005). Cancers classified as undifferentiated completely lacked αvβ3 expression. Furthermore, in undifferentiated and grade 3 carcinomas the three molecules studied exhibited marked distributional heterogeneity with regard to focal positivity and negativity within the same tumor. Either the absence of CAR, αvβ3 and αvβ5 or the pronounced heterogeneity in their expression might seriously compromise the efficiency of adenovirus-based gene therapy in ovarian cancer.

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Acknowledgements

This work was supported in part by a grant from the Fondation Lions Vaincre le Cancer, Luxembourg. The authors thank Mrs Martina Kaindl and Mrs Vera Stivic for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Innsbruck University Hospital, Innsbruck, Austria

    AG Zeimet, E Müller-Holzner, A Schuler, G Hartung, J Berger, M Hermann, M Widschwendter & C Marth

  2. Division of Immunologic and Infectious Diseases, Children's Hospital, Philadelphia, PA, USA

    JM Bergelson

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  1. AG Zeimet
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Zeimet, A., Müller-Holzner, E., Schuler, A. et al. Determination of molecules regulating gene delivery using adenoviral vectors in ovarian carcinomas. Gene Ther 9, 1093–1100 (2002). https://doi.org/10.1038/sj.gt.3301775

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