Immuno-gene therapy for non-small lecclung cancer using innate immunity by NKG2D and its ligand.

利用 NKG2D 及其配体的先天免疫对非小细胞肺癌进行免疫基因治疗。

• 批准号: 13670588
• 负责人: SAIJO Yasuo
• 金额: $ 2.3万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670588/
• 关键词: lung cancer; gene thransfer; NKG2D; RAE-1; Fractalkine; RAE-1; gene therapy; immunotherapy; C26

NKG2D and its ligand, play a crucial role for innate immunity against to tumor. We developed adenoviral vector coding murine NKG2D ligand RAE-1 (Ad.CMV.RAE-1). When mouse colon cancer cells C26 were infected with Ad.CMV.RAE-1, these cells developed slightly slower than control C26 cells. Because RAE-1 showed very limited effects, we also constructed adenoviral vector expressing CX3C chemokine fractalkine (Ad.CMV.FKN). Intratumoral injection of Ad.CMV.FKN strongly suppressed C26 tumor by 65 % and B16 tumor by 82 %. Immunohistochemistry of tumor treated by Ad.CMV.FKN revealed abundant infiltration of NK cells, CD4 T cells, and CD8 T cells. Vaccinations with Ad.CMV.FKN treated B16 cells inhibited tumor growth of wild type B16. These results indicated that CX3C chemokine induced strong anti-tumor immune responses by recruiting NK cells and T lymphocytes.

NKG2D及其配体在抗肿瘤先天免疫中起重要作用。我们开发了腺病毒载体编码小鼠NKG2D配体RAE-1 （Ad.CMV.RAE-1）。小鼠结肠癌细胞C26感染Ad.CMV。RAE-1，这些细胞比对照C26细胞发育稍慢。由于RAE-1的作用非常有限，我们还构建了表达CX3C趋化因子fractalkine （Ad.CMV.FKN）的腺病毒载体。瘤内注射Ad.CMV.FKN对C26和B16的抑制作用分别为65%和82%。经Ad.CMV.FKN处理的肿瘤免疫组化显示大量NK细胞、CD4 T细胞和CD8 T细胞浸润。接种Ad.CMV.FKN处理B16细胞，抑制野生型B16的肿瘤生长。这些结果表明CX3C趋化因子通过募集NK细胞和T淋巴细胞诱导较强的抗肿瘤免疫应答。

项目成果

Iwakami S, Setoguchi Y, Saijo Y, Azuma M, Fukuchi Y.: "Replication-deficient adenovirus-mediated transfer of B7-1 (CD80) cDNA induces anti-tumor immunity in isolated human lung cancer"Respirology. 6. 135-144 (2001)

Iwakami S、Setoguchi Y、Saijo Y、Azuma M、Fukuchi Y.：“复制缺陷型腺病毒介导的 B7-1 (CD80) cDNA 转移在分离的人肺癌中诱导抗肿瘤免疫”呼吸学。

Kazuhiro Usui, Yasuo Saijo, Ko Narumi Shohei Koyama, Makoto Maemondo, Toshiaki Kikuchi, Ryushi Tazawa, Koichi Hagiwara, Yoshitomo Ishibashi, Shigeo Ohta, and Toshihiro Nukiwa.: "N-terminal deletion augments the cell-death inducing activity of BAX in adeno

Kazuhiro Usui、Yasuo Saijo、Ko Narumi Shohei Koyama、Makoto Maemondo、Toshiaki Kikuchi、R​​yushi Tazawa、Koichi Hagiwara、Yoshitomo Ishibashi、Shigeo Ohta 和 Toshihiro Nukiwa。：“N 末端删除增强了腺中 BAX 的细胞死亡诱导活性

Pradono P, Tazawa R Maemondo M, Saijo Y, et al.: "Gene transfer of thronbokisan (TX) A_2 synthase and prostaglandin (PG) I_2 synthase antithetically altered tumor angiogenesis and tumor growth"Cancer Research. 62. 63-66 (2002)

Pradono P、Tazawa R Maemondo M、Saijo Y 等人：“血栓素 (TX) A_2 合酶和前列腺素 (PG) I_2 合酶的基因转移相反地改变了肿瘤血管生成和肿瘤生长”癌症研究。

Saijo Y, Tanaka M, Miki M, et al.: "Proinflammatory Cytokine Interleukin-1β Promotes Tumor Growth of Lewis Lung Carcinoma by Induction of Angiogenic Factors"Journal of Immunology. 169. 469-475 (2002)

Saijo Y、Tanaka M、Miki M 等人：“促炎性细胞因子白细胞介素 1β 通过诱导血管生成因子促进路易斯肺癌的肿瘤生长”《免疫学杂志》169. 469-475 (2002)。

Inoue A, Saijo Y, Maemondo M, et al.: "Severe Acute Interstitial Pneumonia and Gefitinib"Lancet. 361. 137-139 (2003)

Inoue A、Saijo Y、Maemondo M 等人：“严重急性间质性肺炎和吉非替尼”《柳叶刀》。