Cancer Gene Therapy with a Hand-Held Gene Gun

使用手持式基因枪进行癌症基因治疗

• 批准号: 10671129
• 负责人: KOBAYASHI Eiji
• 金额: $ 2.11万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671129/
• 关键词: gene therapy; Gene Gun; local therapy; solid tumor therapy

Using a hand-held gene gun which accelerates DNA-coated microparticles, we examined the effects of interleukin-12 (IL-12) gene transfection on several models of rat solid cancer. AH130 cells were injected into portal vein and ileocecal mesenterium lymph node of Donryu rats, as a liver and lymph node metastatic model, respectively. Yoshida sarcoma cells were injected into the axillar skin lesion. Total amounts of 6 μg of IL-12 DNA coated gold particles were transferred into the liver with metastatic tumors by pressurized helium gas of 300 psi (1 psi=6,890Pa) on day 14 and 16 after the tumor inoculation. Four mg of IL-12 DNA was given into the lymph node metastatic tumor on day 7 and 9 after tumor cell injection skin tumor was bombarded by IL-12 with TNF- α. The corresponding amounts of β -galactosidase were given by the identical route as a control for each group. Compared with the control group, IL-12 gene therapy was statistically effective for the inhibition of tumor growth and for survival rates in the liver metastatic model. A few beneficial effect of IL-12 transduction were observed in the lymph node metastatic model. Skin tumor growth was significantly suppressed by combination of IL-12 with TNF- α. From the standpoint of surgery or surgeons, this method has potential as a new strategy for cancer, especially as an intraoperative gene therapy.

利用手持基因枪加速DNA包裹的微粒，我们检测了白介素12(IL-12)基因对几种实体瘤模型大鼠的影响。将AH130细胞分别注入东丽大鼠门静脉和回盲肠系膜淋巴结，作为肝转移模型和淋巴结转移模型。将吉田肉瘤细胞注射到腋下皮损处。在肿瘤接种后第14天和第16天，用300psi(1psi=6,890Pa.)的加压氦气将总计6μg的IL-12DNA包被金颗粒转移到转移瘤患者的肝脏。在肿瘤细胞注射后第7天和第9天，用IL-12联合肿瘤坏死因子-α轰击皮肤肿瘤，给转移瘤内注射IL-12DNA 4 mg。每组均按相同途径给予相应剂量的β-半乳糖苷酶作为对照。与对照组相比，在肝转移模型中，IL-12基因治疗在抑制肿瘤生长和提高生存率方面具有统计学意义。在淋巴结转移模型中观察到了IL-12转导的一些有益作用。联合应用IL-12和肿瘤坏死因子-α可显著抑制皮肤肿瘤生长。从外科或外科医生的角度来看，这种方法有可能成为癌症的一种新策略，特别是作为术中的基因治疗。

项目成果

Hosoya Y, et al.: "Introduction of cytokine genes into rat solid neoplasm with a hand held gene gun. -I.Combined effect of IL-12 with TNF α gene transfection on subcutaneous tumor-."Ann Cancer Res Ther.. 7. 39-42 (1998)

Hosoya Y 等人：“用手持基因枪将细胞因子基因引入大鼠实体瘤。-I.IL-12 与 TNF α 基因转染对皮下肿瘤的联合作用-”Ann Cancer Res Ther. 7 .39-42 (1998)

小林英司: "Gene gunを用いた遺伝子導入." Sugery Frontier. 6(in press). (1999)

Eiji Kobayashi：“使用基因枪进行基因转移。”（正在出版）。

小林英司 他: "癌免疫療法に対する遺伝子銃の開発と今後の展望."Biotherapy. 12(1). 203-206 (1998)

Eiji Kobayashi 等人：“癌症免疫治疗基因枪的发展和未来前景”。生物治疗 12(1)。

細谷好則 他: "固形癌治療における遺伝子銃応用の展望と問題点."Biotherapy. 13. 418-422 (1999)

Yoshinori Hosoya 等人：“基因枪在实体瘤治疗中应用的前景和问题。”生物治疗。13. 418-422 (1999)

Hosoya Y, et al.: "Induction of cytokine gene into rat neoplasm using a hand help gene gun. II.Local bombardment of IL-12 DNA plasmid on liver metastasis."Ann Cancer Res Ther. (in press).

Hosoya Y 等人：“使用手动基因枪将细胞因子基因诱导到大鼠肿瘤中。II.IL-12 DNA 质粒对肝转移的局部轰击。”Ann Cancer Res Ther。