Melanoma Research Today is a free monthly online journal that collates and summarizes the latest research about Melanoma, including details on identification, causes, prevention, treatment. | ||||||||
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Therapeutic effect of pEgr-IL18-B7.2 gene radiotherapy in B16 melanoma-bearing mice.Yang J, Jin G, Liu X, Liu S Immunobiology Laboratory, MH Radiobiology Research Unit, School of Public Health, Jilin University, Changchun, Jilin 130021, People's Republic of China. 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. Published 2 May 2007 in Hum Gene Ther, 18(4): 323-32.
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