Viral Oncolytic Therapy

The liver is a common site for primary or metastatic disease. In addition to primary liver tumors, such as hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma, several cancers are known to present with isolated hepatic metastasis, including colorectal carcinoma, ocular melanoma, and neuroendocrine cancers. Moreover, in patients with additional sites of extrahepatic disease, it is the hepatic disease burden that is often the cause of morbidity and mortality. Liver resection, liver transplantation, and ablation remain the treatments of choice for prospects of cure; however, many patients are not ideal candidates due to number or size of lesions or other comorbidities. The response rate of primary liver tumors to chemotherapy is low. Interventional oncology approaches including chemotherapy and radioembolization make use intra-arterial access to the liver for delivering therapy. Recent advances in oncolytic viruses, however, offer a new and promising intraarterial therapy. Viral oncolysis broadly refers to the use of modified viruses to infect and subsequently lyse tumor cells. This concept arises from the observation that viral replication is itself effective in destroying tumor cells. This effect is then amplified by reinfection of adjacent tumor cells by the progeny virion released from lysed tumor cells. Herpes simplex virus 1 (HSV-1) has been the primary focus of current efforts in viral oncolysis.1–4 It is a doublestranded DNA virus that is a ubiquitous pathogen transmitted by direct mucosal contact. Infection with HSV-1 is common, reported to be 66 to 84% in the United States. Skin or mucosal infection with HSV-1 is typically followed by transmission via sensory nerves to the trigeminal ganglia where lifelong latent infection occurs. Reactivation from ganglionic neurons may occur resulting in an epithelial ulcer