title: Oncolytic and immunologic cancer therapy with GM-CSF-armed vaccinia virus of Tian Tan strain Guang9.
abstract: Targeted oncolytic vaccinia viruses are being developed as a novel strategy in cancer therapy. Arming vaccinia viruses with immunostimulatory cytokines can enhance antitumor efficacy. Such engineered oncolytic viruses, like JX-594, a Wyeth strain vaccinia virus modified with human granulocyte-macrophage colony-stimulating factor (GM-CSF), have shown promising results and have proceeded rapidly in clinical trials. However, the oncolytic potential of the Chinese vaccine strain Tian Tan (VTT) has not been explored. In this study, we constructed a targeted oncolytic vaccinia virus of Tian Tan strain Guang9 (VG9) expressing murine GM-CSF (VG9-GMCSF) and evaluated the antitumor effect of this recombinant vaccinia virus in a murine melanoma model. In vitro, viral replication and cytotoxicity of VG9-GMCSF was as potent as VG9; in vivo, VG9-GMCSF significantly inhibited the growth of subcutaneously implanted melanoma tumors, prolonged the survival of tumor-bearing mice, and produced an antitumor cytotoxic response. Such antitumor effect may be due to the lytic nature of virus as well as the stimulation of immune activity by GM-CSF production. Our results indicate that VG9-GMCSF induces strong tumoricidal activity, providing a potential therapeutic strategy for combating cancer.
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Deng
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Fan
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Guo
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China. Electronic address: huangbiao@jsinm.org.
authors.forename: Biao
authors.initials: B
authors.lastname: Huang
mesh_terms: D000818:Animals; D002470:Cell Survival; D002522:Chlorocebus aethiops; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D013997:Time Factors; D047368:Tumor Burden; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Antitumor immunity; Cancer therapy; GM-CSF; Oncolytic vaccinia virus; Tian Tan strain Guang9