Oncolytic and immunologic cancer therapy with GM-CSF-armed vaccinia virus of Tian Tan strain Guang9.

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.

Deng L ，Fan J ，Guo M ，Huang B ... -  《-》

Oncolytic efficacy of thymidine kinase-deleted vaccinia virus strain Guang9.

Deng L ，Fan J ，Ding Y ，Zhang J ，Zhou B ，Zhang Y ，Huang B ... -  《Oncotarget》

Oncolytic cancer therapy with a vaccinia virus strain.

Deng L ，Fan J ，Ding Y ，Zhang J ，Zhou B ，Zhang Y ，Huang B ，Hu Z ... -  《-》

IL-24-Armed Oncolytic Vaccinia Virus Exerts Potent Antitumor Effects via Multiple Pathways in Colorectal Cancer.

Deng L ，Yang X ，Fan J ，Ding Y ，Peng Y ，Xu D ，Huang B ，Hu Z ... -  《-》

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

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. 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. 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. 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.

Deng L ，Yang X ，Fan J ，Ding Y ，Peng Y ，Xu D ，Huang B ，Hu Z ... -  《-》