Armed Oncolytic Virus for Treating Cancer

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Introduction: Oncolytic virus (OV) therapy, a type of cancer immunotherapy, provides a new promising strategy for treating cancer. OVs preferentially infect cancer cells and induce tumor-selective cell death, so-called oncolysis. Second-generation OVs with transgene insertions express foreign genes such as immune modulators and cytokines that result in enhanced tumor lysis, and in 2015 the FDA approved the first OV cancer therapy of this type. Concern over tumor resistance to OV-induced immunolysis has been raised for many cancer types, driven predominantly by resistance to apoptosis. A new generation of OVs that overcome this resistance is critically needed. Technology: A Georgia State University inventor has developed an OV to overcome tumor resistance and treat cancers. Smac/DIABLO is a mitochondrial protein known to sensitize tumor cells to OVs by preventing the inhibition of apoptosis. The inventor constructed an armed vesicular stomatitis virus by inserting a transgene to express Smac/DIABLO (VSV-S). During VSV-S infection in breast cancer cells, the level of Smac was enhanced in sharp contrast to wtVSV, resulting in significant tumor cell apoptosis. An in vivo mice study showed that the tumor volume in a human breast cancer xenograft model was significantly reduced � up to 85% � after intratumoral injection of a single dose of VSV-S. More recently, the VSV-S demonstrated significant efficacy in a mouse model against pancreatic cancer cells as well. Based on these studies, this third-generation OV, VSV-S, has dramatically enhanced efficacy to induce programmed cell death without compromising safety in pre-clincial models, providing a novel method to potentially overcome tumor resistance in humans.