Therapeutic effect of pEgr-IL18-B7.2 gene radiotherapy in B16 melanoma-bearing mice.
To evaluate the antitumor role of genes B7.2 and IL18, the radiation-inducible dual-gene coexpression plasmid pEgr-IL18-B7.2 was constructed and its effects on tumor were detected both in vitro and in vivo. After the introduction of pEgr-IL18-B7.2 into B16 melanoma cells, followed by X-ray irradiation, higher expression levels of B7.2 and IL18 compared with control were found both by flow cytometry and enzyme-linked immunosorbent assay. It was shown that even low-dose irradiation was able to induce their expression, which could be tightly regulated either by giving cells different doses of radiation or the same dose at different time points. pEgr-IL18-B7.2 was then packaged with liposome and injected into melanoma tumor-bearing mice. The tumors received 5 Gy of local X-ray irradiation every other day for a total of five treatments. B16 tumor growth slowed significantly when treated with pEgr-IL18-B7.2 plus X-radiation versus either treatment separately. Both 1 and 3 days after the last irradiation the group of mice with combined gene and radiation therapy showed significantly higher tumor necrosis factor (TNF)-alpha secretion in peritoneal macrophages, upregulated splenic cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, and higher interferon (IFN)-gamma secretion than those in either individual treatment group or the control group. The stimulation of host anticancer immunity by increased secretion of IL-18 and upregulated immunogenicity of the tumor cells by increased expression of B7.2 on their surface, in addition to the direct effect of local X-irradiation on the tumor cells, may contribute to the novel effect of the combined therapy.
Yang
Jianzheng
J
Immunobiology Laboratory, MH Radiobiology Research Unit, School of Public Health, Jilin University, Changchun, Jilin 130021, People's Republic of China.
Jin
Guanghui
G
Liu
Xiaodong
X
Liu
Shuzheng
S
D000818:Animals; D051940:B7-2 Antigen / Q000235:genetics*; D003131:Combined Modality Therapy; D015316:Genetic Therapy / Q000379:methods*; D020382:Interleukin-18 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology / Q000528:radiation effects; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000528:radiation effects; D008546:Melanoma, Experimental / Q000532:radiotherapy / Q000628:therapy*; D051379:Mice; D010957:Plasmids / Q000235:genetics; D012878:Skin Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D051940:B7-2 Antigen; C497964:CD86 protein, human; D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha