Abstract

Cancer immunotherapy has seen significant advancements with the use of Oncolytic Viruses (OVs), particularly the Vaccinia virus, delivered intravenously. These viruses selectively infect and lyse tumor cells while also stimulating systemic anti-tumor immune responses. However, intravenous delivery of Vaccinia virus is often hampered by immune cells, especially neutrophils and macrophage cells. One promising strategy to overcome these challenges is targeting the Phosphoinositide 3-Kinase (PI3K) delta pathway in these cells. The PI3K delta pathway plays a major role in the regulation of immune cell functions, including cell activation, differentiation and migration, as well as in the maintenance of immune tolerance. Inhibiting this pathway can enhance anti-tumor immunity by modulating the activity of various immune cell subsets in blood and within the tumor.

Keywords: Cancer immunotherapy; Oncolytic viruses; Macrophage cells; PI3K