ACTIVE SPECIFIC IMMUNOTHERAPY OF PULMONARY METASTASIS WITH VACCINIA MELANOMA ONCOLYSATE PREPARED FROM GRANULOCYTE MACROPHAGE COLONY-STIMULATING-FACTOR-GENE-ENCODED VACCINIA VIRUS/

Vaccinia melanoma oncolysate (VMO) prepared with recombinant vaccinia virus encoding the gene of murine granulocyte/macrophage-colony-stimul ating factor (GM-CSF) was tested for its therapeutic effect on melanom a pulmonary metastasis. The murine pulmonary metastasis model was esta blished by injecting 2 x 10(5) B16F10 melanoma cells into the tail vei n of a C57BL/6 mouse, Intraperitoneal injection of VMO was performed i n tumor-bearing mice 3 and 10 days after B16F10 cell inoculation. The results showed that treatment with VMO prepared with GM-CSF-gene-encod ed vaccinia virus (GM-CSFVMO) significantly decreased the number of mu rine pulmonary metastases and prolonged the survival of the tumor-bear ing mice. Lymphocytes isolated from fresh blood and spleen of GM-CSFVM O-treated mice showed higher cytolytic activity against B16F10 melanom a cells when compared with lymphocytes from the mice of other treatmen t groups. Natural killer activity remained unchanged in the GM-CSFVMO- treated group. Cytotoxic activities of peritoneal macrophages were fou nd to be greatly elevated in mice treated with GM-CSFVMO. Further stud y illustrated that the increased tumor necrosis factor and nitric oxid e 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 lymp hocytes and macrophages.