Therapeutic effect of gene-therapy in combination with local X-irradiation in a mouse malignant melanoma model.
Plasmid containing mIL-18 and B7.1 genes downstream of Egr-1 promoter was constructed and used in gene-radiotherapy on malignant melanoma in C57BL/6J mice implanted with B16 cells followed by exploration of the immunologic mechanism of the therapeutic effect. The treatment with plasmid pEgr-IL-18-B7.1 plus local X-irradiation showed more effective suppression of tumor growth than the treatment with radiation alone, pEgr-IL-18-B7.1 alone, or single gene pEgr-IL-18 (or pEgr-B7.1) combined with local X-irradiation. Anticancer immunity was found to be significantly upregulated in tumor-bearing mice treated with pEgr-IL-18-B7.1 plus local X-irradiation. IL-18 showed no direct killing effect on malignant melanoma cells in vitro, and the mechanism of the combined therapy with pEgr-IL-18-B7.1 and local X-irradiation was apparently related with the stimulation of host anticancer immunity by increased secretion of IL-18 and upregulated immunogenicity of the tumor cells by increased expression of B7.1 on their surface in addition to the direct effect of local X-irradiation on the tumor cells.
Jin
Guang-Hui
GH
Immunobiology Laboratory, MH Radiobiology Research Unit, Jilin University Norman, Bethune Health Sciences Center, 828 Xinmin Street, Changchun 130021, PR China.
Jin
Shun-Zi
SZ
Liu
Yang
Y
Xu
Rui-Ming
RM
Yang
Jian-Zheng
JZ
Pan
Xue-Na
XN
Liu
Shu-Zheng
SZ
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects
D018122:B7-1 Antigen; D020382:Interleukin-18