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Enhancing Radiotherapy With Genetically Engineered Viruses

Sunil J. Advani, Ralph R. Weichselbaum, Steven J. Chmura

From the Departments of Radiation and Cellular Oncology, Center for Molecular Medicine, University of Chicago, Chicago, IL

Address reprint requests to Steven Chmura, MD, PhD, Department of Radiation and Cellular Oncology, The University of Chicago Hospitals, Mail Code 9006, 5758 S Maryland Ave, Chicago, IL 60637; e-mail: schmura{at}radonc.uchicago.edu

Concurrent radiotherapy and chemotherapy have been used to treat a variety of tumors to improve local control and overall survival. Gene therapy strategies represent a novel means to further improve the therapeutic ratio of ionizing radiation. Cancer gene therapy strategies in clinical trials include the use of replication-defective shuttle vectors to deliver exogenous genes and replication-competent oncolytic viruses. This review focuses on these approaches in the context of radiotherapy and radiochemotherapy. In the shuttle vector approach, exogenous gene products that enhance ionizing radiation–mediated tumor cell destruction have been selected. Moreover, the expression of exogenous genes encoding therapeutic proteins can be regulated through the use of ionizing radiation–enhanced promoters. Also, genetically engineered attenuated replication-competent viruses have been investigated in clinical trials. Preclinical data indicate that ionizing radiation interacts with replication-competent oncolytic viruses to enhance viral replication and tumor destruction. Here, we review the background preclinical and current clinical data utilizing gene therapy with radiotherapy.

Supported by National Institutes of Health Grant Nos. RO1 CA 111423 and PO1 CA 71933-07.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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