Cell carriers for systemic delivery of oncolytic viruses

Abstract

There is a clear need for novel therapeutics that can improve the treatment of metastatic cancers. Conditionally replicative oncolytic viruses represent one promising class of new agents that have garnered recent attention in laboratory and clinical studies. While much success has been achieved in targeting the replication and cytolytic effects of viruses to tumor cells, systemic delivery remains a major challenge. We have developed a murine tumor model in order to investigate potential obstacles to systemic delivery of oncolytic viruses in an immunocompetent host. We find that the in vivo delivery of naked virus particles to tumors is ablated by the humoral antiviral response elicited during repeated therapeutic administration. In contrast, live cell carriers avoid neutralization and deliver oncolytic virus to tumor beds in the presence of high-titer circulating antibodies. We investigated the properties of various mammalian cell lines as oncolytic virus carriers, and conclude with studies of a novel insect cell carrier system. The unique properties of this insect cell carrier platform make it an attractive technology for immediate clinical use as well as continued refinement in the lab.