Construction and analysis of new vector systems with improved interleukin-18 secretion in a xenogeneic human tumor model

被引：7

作者：

Goto, H

Osaki, T

Nishino, K

Tachibana, I

Takeda, Y

Yoneda, T

Funakoshi, T

Kimura, H

Hayashi, S

Tahara, T

机构：

[1] Osaka Univ, Grad Sch Med, Dept Mol Med, Suita, Osaka 5650871, Japan

[2] Univ Tokyo, Inst Med Sci, Dept Surg, Tokyo, Japan

来源：

JOURNAL OF IMMUNOTHERAPY | 2002年 / 25卷

关键词：

interleukin-18; gene therapy; cancer therapy; viral vector; peritoneal exuding cell;

D O I：

10.1097/00002371-200203001-00006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Interleukin (IL)-18 plays an important role in enhancing cellular immunity against cancer and bacteria. We constructed retroviral and adenoviral vectors that show improved secretion of bioactive murine IL-18 that could further enhance antitumor immunity in a murine model. Secretion of bioactive IL-18 was facilitated by fusing the leader sequences of prepro-parathyroid hormone (PTH) or IL-1 receptor antagonist (IL-1ra) to the 5' end of the mature marine IL-18 cDNA. Transfectants established by the retroviral vector carrying IL-1ra/IL-18 hybrid showed about 100-fold more IL-18 production and interferon (IFN)-gamma induction from splenocytes when compared With those carrying PTH/IL-18 hybrid. Repeated intraperitoneal injection of an adenoviral vector with IL-1ra/IL-18 hybrid ligated to IL-18 (Ad.IL-1ra.IL-18) successfully prevented establishment of human colon cancer cells in the abdominal cavity of mice. Treatment with Ad.IL-1ra.11-48 was associated with significantly elevated levels of serum IL-18 and IFN-gamma. IL-18 administration also enhanced the cytostatic activity of peritoneal exudate cells against cancer cells. These improved viral vectors, which efficiently produce bioactive IL-18, could be used as a useful tool for cancer gene therapy.

引用

页码：S35 / S41

页数：7

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