Figure 9.

Proposed mechanism for GM-CSF conditioning to enhance systemic reovirus therapy. (a) Monocyte/macrophages are activated by GM-CSF to upregulate expression of Fc receptors. After systemic delivery of reovirus in an immunized animal, reovirus is bound by anti-reovirus NAb, forming complexes that are loaded onto monocytes/macrophages via binding to their Fc receptors. Increased trafficking of macrophages, induced by GM-CSF, facilitates their delivery to tumors where the virus is handed off for infection of tumor cells. (b) Tumor cell killing is effected by two mechanisms. Once handed off from macrophages, the virus infects and replicates within the tumor, leading to oncolysis and release of new viral particles. In addition, GM-CSF-activated macrophages traffic to tumors, where they bind newly released, tumor-associated reovirus via upregulated Fc receptors. Macrophage–NK interactions at the tumor site promote increased tumor cell killing.