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BioMed Research International
Volume 2017 (2017), Article ID 3620510, 14 pages
https://doi.org/10.1155/2017/3620510
Research Article

Recombinant Vaccinia Viruses Coding Transgenes of Apoptosis-Inducing Proteins Enhance Apoptosis But Not Immunogenicity of Infected Tumor Cells

1Department of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia
2Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia
3Department of Viral Hepatitis, State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, Koltsovo, Russia

Correspondence should be addressed to Olga Koval; ur.sgn@lavok_o

Received 25 April 2017; Revised 17 July 2017; Accepted 26 July 2017; Published 30 August 2017

Academic Editor: Steven De Vleeschouwer

Copyright © 2017 Olga Koval et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Genetic modifications of the oncolytic vaccinia virus (VV) improve selective tumor cell infection and death, as well as activation of antitumor immunity. We have engineered a double recombinant VV, coding human GM-CSF, and apoptosis-inducing protein apoptin (VV-GMCSF-Apo) for comparing with the earlier constructed double recombinant VV-GMCSF-Lact, coding another apoptosis-inducing protein, lactaptin, which activated different cell death pathways than apoptin. We showed that both these recombinant VVs more considerably activated a set of critical apoptosis markers in infected cells than the recombinant VV coding GM-CSF alone (VV-GMCSF-dGF): these were phosphatidylserine externalization, caspase-3 and caspase-7 activation, DNA fragmentation, and upregulation of proapoptotic protein BAX. However, only VV-GMCSF-Lact efficiently decreased the mitochondrial membrane potential of infected cancer cells. Investigating immunogenic cell death markers in cancer cells infected with recombinant VVs, we demonstrated that all tested recombinant VVs were efficient in calreticulin and HSP70 externalization, decrease of cellular HMGB1, and ATP secretion. The comparison of antitumor activity against advanced MDA-MB-231 tumor revealed that both recombinants VV-GMCSF-Lact and VV-GMCSF-Apo efficiently delay tumor growth. Our results demonstrate that the composition of GM-CSF and apoptosis-inducing proteins in the VV genome is very efficient tool for specific killing of cancer cells and for activation of antitumor immunity.