Potentiated Gene Delivery to Tumors Using Herpes Simplex Virus/Epstein-Barr Virus/RV Tribrid Amplicon Vectors

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Abstract
The development and use of gene transfer techniques creates an opportunity to achieve better treatment modalities for numerous disease entities. Promising results for treatment in tumor cells in culture and in small animal models have been reported. Nevertheless, the lack of widespread vector distribution throughout tumor tissue is one of the current limitations for successful clinical application of gene therapy paradigms. The use of migratory tumor cells themselves as vector delivery vehicles may allow wider vector distribution in tumors. In addition, continuous release of retrovirus vectors on-site could generate a high local virion concentration over an extended time period with consequent increases in transduction efficiency. In this paper, we present in culture and in vivo data of a herpes simplex virus-Epstein-Barr virus hybrid amplicon vector containing retrovirus vector components (tribrid vector) that allows conversion of tumor cells into retroviral producer cells. With this method, we were able to achieve a local fourfold amplification of stable transgene expression in tumors. The application of this system, which can integrate a transgene cassette into tumors with therapeutic bystander effects, could increase the local amplification effect to a level of clinical relevance.