Systemic Delivery of Oncolytic Viruses: Hopes and Hurdles

Figure 1

Hurdles of systemic delivery of oncolytic viruses to tumour cells. After intravenous injection, viruses are neutralised by pre-existing antibodies and complement activation. Oncolytic viruses also interact with blood cells. Sequestration into other organs and the reticuloendothelial system is a particular problem, often with resulting toxicities. Macrophages in the lung, liver (aka kupffer cells), and spleen are major players to clear oncolytic viruses after systemic delivery. From the blood stream, viruses have to pass through a mixture of extracellular matrix and cells (including normal and immune cells) before reaching the tumour. The connective tissue of the tumour matrix is important in the regulation and creation of the tumour vasculature; the tumour vasculature itself and interstitial pressures are also key factors involved in the ability of the virus to penetrate the tumour mass.