An Oncolytic Vaccinia Virus Armed with GM-CSF and IL-24 Double Genes for Cancer Targeted Therapy

OncoTargets and Therapy

关键词: oncolytic vaccinia virus;    cancer therpay;    gm-csf;    il-24;    immunotherapy;   

DOI  :  

来源: DOAJ

【 摘 要 】

Lili Deng,1 Xue Yang,2 Jun Fan,1 Yuedi Ding,1 Ying Peng,1 Dong Xu,1 Biao Huang,3 Zhigang Hu2 1NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, People’s Republic of China; 2Wuxi Children’s Hospital, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, People’s Republic of China; 3School of Life Science, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, People’s Republic of ChinaCorrespondence: Zhigang Hu; Biao Huang Email [e-mail]; [e-mail]: Targeted oncolytic vaccinia virus is an attractive candidate for cancer therapy due to its replication causing lysis of infected tumor cells as well as a delivery vector to overexpress therapeutic transgenes. This study constructed a novel oncolytic vaccinia virus carrying granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-24 (IL-24) double genes to improve efficacy for cancer therapy.Methods: Vaccinia virus co-expressing GM-CSF and IL-24 based on Chinese Guang9 strain (VG9-GMCSF-IL24) was constructed with disruption of the viral thymidine kinase (TK) gene. The cytotoxicity of VG9-GMCSF-IL24 in various cell lines was assessed by MTT. The synergistic antitumor effect of VG9-GMCSF-IL24 in vivo was assessed on multiple tumor models.Results: In vitro cytotoxicity assay showed that VG9-GMCSF-IL24 exerted a strongly cytotoxic effect on cancer cells, but with no significant cytotoxicity to normal cells. Significant tumor growth inhibition and prolonged survival were observed in different tumor models treated with VG9-GMCSF-IL24. Additionally, systemic and specific antitumoral immunity was investigated in vivo, and enhanced antitumor immunity was observed in VG9-GMCSF-IL24-treated mice.Conclusion: Our results indicated that VG9-mediated GM-CSF and IL-24 co-expression performed cooperative and overlapping antitumor effect. As a novel and effective therapeutic strategy for cancer, the combination of oncolysis and immunotherapy with vaccinia virus carrying one or more immunostimulatory genes may have a satisfactory clinical application prospect.Keywords: oncolytic vaccinia virus, cancer therapy, GM-CSF, IL-24, immunotherfapy

【 授权许可】

Unknown