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. 1996 Dec;122(12):716–722. doi: 10.1007/BF01209118

Active specific immunotherapy of pulmonary metastasis with vaccinia melanoma oncolysate prepared from granulocyte/macrophage-colony-stimulating-factor-gene-encoded vaccinia virus

Dian Wen Ju 1, Xuetao Cao 1,✉, Bruce Acres 2
PMCID: PMC12200445  PMID: 8954168

Abstract

Vaccinia melanoma oncolysate (VMO) prepared with recombinant vaccinia virus encoding the gene of murine granulocyte/macrophage-colony-stimulating factor (GM-CSF) was tested for its therapeutic effect on melanoma pulmonary metastasis. The murine pulmonary metastasis model was established by injecting 2×105 B16F10 melanoma cells into the tail vein of a C57BL/6 mouse. Intraperitoneal injection of VMO was performed in tumor-bearing mice 3 and 10 days after B16F10 cell inoculation. The results showed that treatment with VMO prepared with GM-CSF-geneencoded vaccinia virus (GM-CSFVMO) significantly decreased the number of murine pulmonary metastases and prolonged the survival of the tumor-bearing mice. Lymphocytes isolated from fresh blood and spleen of GM-CSFVMO-treated mice showed higher cytolytic activity against B16F10 melanoma cells when compared with lymphocytes from the mice of other treatment groups. Natural killer activity remained unchanged in the GM-CSFVMO-treated group. Cytotoxic activities of peritoneal macrophages were found to be greatly elevated in mice treated with GM-CSFVMO. Further study illustrated that the increased tumor necrosis factor and nitric oxide release from macrophages may contribute to their cytotoxic effects. These results suggest that the tumor oncolysate vaccine prepared with GM-CSF-gene-encoded vaccinia virus has a potent therapeutic effect on tumor metastasis through the efficient induction of antitumor immunity of the host, mainly through the cytotoxic effects of cytotoxic T lymphocytes and macrophages.

Key words: Recombinant vaccinia virus, GM-CSF, Melanoma, Gene therapy, Macrophage, Metastasis

Abbreviations

GM-CSFVMO

vaccinia melanoma oncolysate (VMO) prepared with granulocyte/macrophage-colony-stimulating-factor-gene-encoded vaccinia virus

TKVMO VMO

prepared with thymidine-kinase (TK)-gene-deficient vaccinia virus

IL

interleukin

FCS

fetal calf serum

TNF

tumor necrosis factor

CTL

cytotoxic T lymphocytes

Footnotes

This work was supported by a grant from the National Natural Science Foundation of China

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