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SurvivinT34A 和 FilC 的异位表达可增强痘苗病毒在小鼠胃癌中的溶瘤作用
Authors Wang M, Luo Y, Sun T, Mao C, Jiang Y, Yu X, Li Z, Xie T, Wu F, Yan H, Teng L
Received 13 September 2019
Accepted for publication 16 January 2020
Published 3 February 2020 Volume 2020:13 Pages 1011—1025
DOI https://doi.org/10.2147/OTT.S230902
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Yong Teng
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.
Keywords: vaccinia virus WR strain, survivin T34A, FilC, anti-tumor effect
