Intravenous Injections of a Rationally Selected Oncolytic Herpes Virus as a Potent Virotherapy for Hepatocellular Carcinoma.

ABSTRACT

As a clinical setting in which novel treatment options are urgently needed, hepatocellular carcinoma (HCC) exhibits intriguing opportunities for oncolytic virotherapy. Here we report the rational generation of a novel herpes simplex virus type 1 (HSV-1)-based oncolytic vector for targeting HCC, named Ld0-GFP, which was derived from oncolytic ICP0-null virus (d0-GFP), had a fusogenic phenotype, and was a novel killer against HCC as well as other types of cancer cells. Compared with d0-GFP, Ld0-GFP exhibited superior cancer cell-killing ability in vitro and in vivo. Ld0-GFP targets a broad spectrum of HCC cells and can result in significantly enhanced immunogenic tumor cell death. Intratumoral and intravenous injections of Ld0-GFP showed effective antitumor capabilities in multiple tumor models, leading to increased survival. We speculated that more active cell-killing capability of oncolytic virus and enhanced immunogenic cell death may lead to better tumor regression. Additionally, Ld0-GFP had an improved safety profile, showing reduced neurovirulence and systemic toxicity. Ld0-GFP virotherapy could offer a potentially less toxic, more effective option for both local and systemic treatment of HCC. This approach also provides novel insights toward ongoing efforts to develop an optimal oncolytic vector for cancer therapy.