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

Olga Koval, Galina Kochneva, Anastasiya Tkachenko, Olga Troitskaya, Galina Sivolobova, Antonina Grazhdantseva, Anna Nushtaeva, Elena Kuligina, Vladimir Richter

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Article number3620510
Pages (from-to)3620510
Number of pages14
JournalBioMed Research International
Publication statusPublished - 1 Jan 2017


  • Animals
  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins/genetics
  • Apoptosis/genetics
  • Biomarkers, Tumor/genetics
  • Caspase 3/genetics
  • Caspase 7/genetics
  • Cell Death/genetics
  • Cell Line, Tumor
  • Cercopithecus aethiops
  • DNA Fragmentation
  • Female
  • Genetic Vectors/genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor/genetics
  • HSP70 Heat-Shock Proteins/genetics
  • Humans
  • Membrane Potential, Mitochondrial/genetics
  • Mice
  • Mice, SCID
  • Neoplasms/genetics
  • Oncolytic Viruses/genetics
  • Phosphatidylserines/genetics
  • Transgenes/genetics
  • Up-Regulation/genetics
  • Vaccinia virus/genetics
  • Virus Replication/genetics
  • bcl-2-Associated X Protein/genetics

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