Enhancing radiotherapy with genetically engineered viruses.
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.
Advani
Sunil J
SJ
Department of Radiation and Cellular Oncology, Center for Molecular Medicine, University of Chicago, Chicago, IL, USA.
Weichselbaum
Ralph R
RR
Chmura
Steven J
SJ
D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy* / Q000628:therapy; D014780:Viruses / Q000235:genetics*