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[Cancer Research 62, 1266-1270, March 1, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Treatment of Ovarian Cancer with a Tropism Modified Oncolytic Adenovirus1

Gerd J. Bauerschmitz, John T. Lam, Anna Kanerva, Kaori Suzuki, Dirk M. Nettelbeck, Igor Dmitriev, Victor Krasnykh, Galina V. Mikheeva, Mack N. Barnes, Ronald D. Alvarez, Peter Dall, Ramon Alemany, David T. Curiel and Akseli Hemminki2

Division of Human Gene Therapy, Departments of Medicine, Pathology, and Surgery [G. J. B., J. T. L., A. K., K. S., D. M. N., I. D., V. K., R. D. A., D. T. C., A. H.] and Division of Gynecology Oncology, Department of Obstetrics and Gynecology [M. N. B., R. D. A.], University of Alabama at Birmingham, Birmingham, Alabama 35294-3300; VectorLogics, Inc., Birmingham, Alabama 35233 [V. K., G. V. M.]; Duesseldorf University Medical Center, Department of Obstetrics and Gynecology, Heinrich-Heine University, 40225 Duesseldorf, Germany [P. D.]; and Gene Therapy Unit, Institut Catala d’Oncologia, 08907 Barcelona, Spain [R. A.]

Ad5-{Delta}24RGD is an adenovirus that is selectively replication competent in cells defective in the Rb/p16 pathway, such as ovarian cancer cells. The fiber of Ad5-{Delta}24RGD contains an integrin binding RGD-4C motif, allowing Coxsackie adenovirus receptor-independent infection of cancer cells. Oncolysis of cell lines was similar to that of a wild-type control, and replication in primary tumor material was shown using a novel three-dimensional spheroid model. Finally, an orthotopic murine model of peritoneally disseminated ovarian cancer was used to test i.p. administration to tumor-bearing animals. Injection of the agent resulted in eradication of i.p. disease, whereas control animals expired (P < 0.0001). These results suggest that Ad5-{Delta}24RGD could be useful for treatment of ovarian cancer in humans.




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