Apoptin enhances the oncolytic properties of vaccinia virus and modifies mechanisms of tumor regression

// Galina Kochneva 1, 2 , Evgeniy Zonov 3 , Antonina Grazhdantseva 2 , Anastasiya Yunusova 1, 3 , Galina Sibolobova 2 , Evgeniy Popov 1, 2 , Oleg Taranov 2 , Sergei Netesov 1, 2 , Peter Chumakov 1, 4 , Elena Ryabchikova 1, 3 1 Novosibirsk State University, Novosibirsk, Russia 2 State Research Center of Virology and Biotechnology “Vector”, Koltsovo, Russia 3 Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia 4 Engelhardt Institute of Molecular Biology, Moscow Correspondence to: Elena Ryabchikova, e-mail: lenryab@yandex.ru Sergei Netesov, e-mail: nauka@nsu.ru Keywords: Vaccinia virus, apoptin expressing recombinant, oncolytic properties, carcinoma A431 Received: July 15, 2014 Accepted: October 08, 2014 Published: November 19, 2014 ABSTRACT A recombinant vaccinia virus VVdGF-ApoS24/2 expressing apoptin selectively kills human cancer cells in vitro [Kochneva et al., 2013]. We compared the oncolytic activity of this recombinant with that of the parental strain L-IVP using a model of human A431 carcinoma xenografts in nude mice. Single intratumoral injections (2×10 7 PFU/mouse) of the viruses produced a dramatic decrease in tumor volumes, which was higher after injection of apoptin-producing virus. The tumor dried out after the injection of recombinant while injection of L-IVP strain resulted in formation of cavities filled with cell debris and liquid. Both viruses rapidly spread in xenografts and replicate exclusively in tumor cells causing their destruction within 8 days. Both viruses induced insignificant level of apoptosis in tumors. Unlike the previously described nuclear localization of apoptin in cancer cells the apoptin produced by recombinant virus was localized to the cytoplasm. The apoptin did not induce a typical apoptosis, but it rather influenced pathway of cell death and thereby caused tumor shrinkage. The replacement of destroyed cells by filamentous material is the main feature of tumor regression caused by the VVdGF-ApoS24/2 virus. The study points the presence of complicated mechanisms of apoptin effects at the background of vaccinia virus replication.