Fundamental Study of Gene Therapy for Renal Cell Carcinoma Using IL-12

IL-12肾细胞癌基因治疗的基础研究

• 批准号: 08671816
• 负责人: NAKAMOTO Takahisa
• 金额: $ 1.41万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671816/
• 关键词: Renal Cell Carcinoma; Gene Therapy; IL-12

Interleukin-12 (IL-12) is expected a cytokine which can induce a potent antitumor effect. To determine the possibility of IL-12 for gene therapy of renal cell carcinoma, we prepared genetically engineered murine renal cell carcinoma to secrete IL-12 using MFG retroviral vector. Renca IL-12 can secrete 146.7ng of bioactive IL-12/ml/1x10^6cell/48 hr. In vivo tumorigenecity of Renca IL-12 reduced significantly compared with Renca wild and lac Z,whereas in vitro growth and surface antigen, such as MHC class I,class II,or B7-1, of each cells did not alter. These results suggested that antitumor immune response induced by high concentration of IL-12 in local site might be responsible for loss of tumorigenecity of Renca IL-12. Renca IL-12 also inhibited the growth of Renca wild at a distant site. Furthermore, some mice rejected inoculated Renca IL-12 were determined to be immune to a rechallenge of Renca wild. We believe that these results support the feasibility of IL-12 gene therapy for the treatment of renal cell carcinoma.

白细胞介素-12 （IL-12）被认为是一种具有抗肿瘤作用的细胞因子。为了确定IL-12用于肾细胞癌基因治疗的可能性，我们利用MFG逆转录病毒载体制备了基因工程小鼠肾细胞癌，使其分泌IL-12。Renca IL-12可分泌146.7ng生物活性IL-12/ml/1x10^6细胞/48小时。与野生的Renca和lac Z相比，Renca IL-12的体内致瘤性显著降低，而每种细胞的体外生长和表面抗原（如MHC I类，II类或B7-1）没有改变。这些结果提示，局部高浓度IL-12诱导的抗肿瘤免疫应答可能是Renca IL-12致瘤性丧失的原因。Renca IL-12也在远处抑制了Renca野生植株的生长。此外，一些被拒绝接种Renca IL-12的小鼠被确定对Renca野生病毒的再攻击具有免疫力。我们认为这些结果支持IL-12基因治疗肾细胞癌的可行性。

项目成果

T. Nakamoto: "Loss of tumorigenecity induced by interleukin-12 gene transferin murine renal cell carcinoma cells" Proceeding of the American Association for Cancer Research. 38. 11 (1997)

T. Nakamoto：“小鼠肾细胞癌细胞中白细胞介素 12 基因转移诱导的致瘤性丧失”美国癌症研究协会会刊。

中本貴久: "腎細胞癌に対するIL-12遺伝子治療の基礎的研究.I.IL-12遺伝子導入細胞の作製" Biotherapy. 11・3. 290-292 (1997)

Takahisa Nakamoto：“肾细胞癌IL-12基因治疗的基础研究。I.IL-12基因转染细胞的制备”生物疗法11・3（1997）。

T.Nakamoto: "Loss of tumorigenecity induced by interleukin-12 gene transferin murine renal cell carcinoma cells." Proceeding of the American Association for Cancer Research. 38. 11 (1997)

T.Nakamoto：“白细胞介素 12 基因转入鼠肾细胞癌细胞中诱导致瘤性丧失。”

中本貴久,他: "腎細胞癌に対するIL-12遺伝子の基礎的研究.IL-12遺伝子導入細胞の作成" Biotherapy. 11 (3). 290-292 (1997)

Takahisa Nakamoto等人：“肾细胞癌IL-12基因的基础研究。IL-12基因转染细胞的创建”生物疗法11(3)(1997)。

Kasaoka, Y.: "Gene therapy for murine renal cell carcinoma using IL-12." Proceedings of a Study Group against Renal Cancer. 14 (in press). (1998)

Kasaoka, Y.：“使用 IL-12 对小鼠肾细胞癌进行基因治疗。”