Original Article


ANTITUMOR EFFECT OF GRANULOCYTE-MACROPHAGE COLONY- STIMULATING FACTOR (GM-CSF)-GENE ENCODED VACCINIA MELANOMA ONCOLYSATE AND ITS IMMUNOLOGICAL MECHANISMS1

Dianwen Ju, Xuetao Cao, Tao Wan, Weiping Zhang, Qun Tao, Yizhi Yu, Guoyou Chen

Abstract

Vaccinia melanoma oncolysate (VMO) prepared by infecting B16F10 melanoma cells with recombinant vaccinia virus encoding murine GM-CSF gene was tested for its therapeutic effect on the preestablished melanoma. C57BL/6 mice were inoculated s.c. with 1 × l05 B16F10 melanoma cells and received s.c. administration with VMO prepared with GM-CSF gene-encoded vaccinia virus(GM-CSFVMO), VMO prepared with thymidine kinase gene-deficient vaccinia virus(TKVMO), B16F10 melanoma oncolysate(BMO), or PBS 3 days after tumor inoculation. The same treatment was bolstered one week later. The results demonstrated that GM-CSFVMO treatment significantly inhibited the growth of subcutaneous tumor and prolonged the survival period of tumor-bearing mice. Further study elucidated that cytotoxicity of PBL and splenocytes towards B16F10 increased obviously after treatment with GM-CSFVMO, but NK activity remained unchanged. These results suggest that the tumor oncolysate vaccine prepared with GM-CSF gene-encoded vaceinia virus might exert potent therapeutic effect on the preestablished tumor through the efficient induction of specific antitumor immune response of the host.