The ectopic expression of survivin T34A and filc can enhance the oncolytic effects of vaccinia virus in murine gastric cancer

Abstract

Background/Aims: Anti-tumor vaccines have been shown to be effective in cancer therapeutics ever since the anti-HPV vaccine was developed. Compared to conventional chemotherapy, anti-tumor vaccines can specifically target cancer cells and they have lower side effects. We developed a recombinant vaccinia virus (VACV) (Western Reserve) WR strain, and we tested its anti-tumor effects in an animal model. Methods: A recombinant VACV WR strain expressing mutant survivin T34A (SurT34A) and FilC was constructed and validated. Its oncolytic effect was tested in vitro using a CCK-8 assay, and its tolerance and anti-tumor effects were tested in a murine gastric cancer model. The proportion of lymphocytes in the spleen and tumor was determined after antibody-mediated immuno-depletion. Results: The recombinant VACV showed a stronger replication ability in tumor cells, and it was safe in vivo, even at high doses. The combination of vv-SurT34A and vv-FilC resulted in a stronger anti-tumor effect compared to either construct alone. However, the inhibitory effect of vv-SurT34A was stronger than the combination. The recombinant VACV activated the host immune response, as indicated by lymphocyte infiltration in the spleen and tumor tissues. Conclusion: The recombinant VACV WR strain expressing SurT34A and FilC is a safe and effective anti-tumor vaccine.