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Antitumor efficacy of oncolytic herpes simplex virus adsorbed onto antigen-specific lymphocytes
Authors:Kanzaki A  Kasuya H  Yamamura K  Sahin T T  Nomura N  Shikano T  Shirota T  Tan G  Fukuda S  Misawa M  Nishikawa Y  Yamada S  Fujii T  Sugimoto H  Nomoto S  Takeda S  Kodera Y  Nakao A
Affiliation:Department of Surgery II, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Abstract:Although several studies have reported that locally administering oncolytic viruses effectively targets malignancies, the efficacy of systemically administered oncolytic viruses is restricted. Recently, however, it was reported that systemic administration of oncolytic vesicular stomatitis virus adsorbed onto antigen-specific lymphocytes was effective against malignancies. We hypothesized that intravenously administering such virus might have significant potential in treatment of the malignant tumors. We adsorbed oncolytic herpes simplex virus-1 mutant R3616 onto lymphocytes harvested from mice with acquired antitumor immunity. We administered adsorbed R3616 to peritoneally disseminated tumors and analyzed the efficacy of this treatment. Mice administered adsorbed R3616 survived significantly longer than mice administered R3616 adsorbed onto non-specific lymphocytes, or mice administered either virus or tumor antigen-specific lymphocytes alone. In this context, herpes oncolytic virus is a promising treatment not only for primary lesions, but also for multiple metastasizing lesions. This treatment strategy may become one of the most effective methods for systemic virus delivery.
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