Development of a novel cancer therapy using soluble T-cell receptor

使用可溶性 T 细胞受体开发新型癌症疗法

• 批准号: 23659489
• 负责人: YASUKAWA Masaki
• 金额: $ 2.41万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659489/
• 关键词: 免疫療法; 遺伝子治療; 細胞傷害性T細胞; T細胞レセプター; 白血病; 細胞障害性Ｔ細胞; Ｔ細胞レセプター; がん免疫療法; WT1; Aurora-A kinase

In this study, we attempted to establish a novel immunotherapyfor cancer using tumor antigen-specific soluble T-cell receptor (TCR). The data obtained from the series of experiments are follows.1) WT1, hTERT, and Aurora-A kinase-derived peptide-specific cytotoxic T cell (CTL) clones were established.2) TCR genes were isolated from these CTL clones.3) A novel retrovirus vector expressing TCR genes and inhibiting expression of endogenous TCR has been developed.4) WT1-specific hTERT-specific, and Aurora-A kinase-specific TCR gene-transduced T cells showed antigen-specific cytotoxicity and exerted anti-leukemia effects in vitro and in vivo.Now, we areattempting to produce WT1-specific soluble TCR molecules.

在本研究中，我们试图利用肿瘤抗原特异性可溶性T细胞受体（TCR）建立一种新的肿瘤免疫治疗方法。从一系列实验中获得的数据如下：1）建立了WT 1、hTERT和Aurora-A激酶衍生的肽特异性细胞毒性T细胞（CTL）克隆; 2）从这些CTL克隆中分离TCR基因; 3）已经开发了表达TCR基因并抑制内源性TCR表达的新型逆转录病毒载体; 4）WT 1特异性hTERT特异性，Aurora-A激酶特异性TCR基因转导的T细胞具有抗原特异性的细胞毒活性，并在体内外发挥抗白血病作用。

项目成果

Activation of T-cell receptor signaling in peripheral T-cell lymphoma cells plays an important role in the development of lymphoma-associated hemophagocytosis

• DOI: 10.1007/s12185-010-0758-7
• 发表时间: 2011-02-01
• 期刊: INTERNATIONAL JOURNAL OF HEMATOLOGY
• 影响因子: 2.1
• 作者: An, Jun;Fujiwara, Hiroshi;Yasukawa, Masaki
• 通讯作者: Yasukawa, Masaki

Novel causative and neutral mutations in a patient with protein C deficiency

蛋白 C 缺乏症患者的新致病突变和中性突变

• DOI: 10.1016/j.thromres.2013.01.021
• 发表时间: 2013
• 期刊: Thrombosis Research
• 影响因子: 7.5
• 作者: Tauchi T;Ashihara E;Ohyasiki K;et al.;Yamanouchi J et al.
• 通讯作者: Yamanouchi J et al.

Lysophosphatidylcholine enhances the suppressive function of human naturally occurring regulatory T cells through TGF-β production

• DOI: 10.1016/j.bbrc.2011.10.119
• 发表时间: 2011-11-25
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Hasegawa, Hitoshi;Lei, Jin;Yasukawa, Masaki
• 通讯作者: Yasukawa, Masaki

Human Telomerase Reverse Transcriptase-Specific T-Cell Receptor Gene Transfer Redirects T-Lymphocytes to Exert Effective Antitumor Reactivity Against Adult T-Cell Leukemia

人端粒酶逆转录酶特异性 T 细胞受体基因转移重定向 T 淋巴细胞，对成人 T 细胞白血病发挥有效的抗肿瘤反应

• 发表时间: 2011
• 作者: Miyazaki Y;Yasukawa M;et al.
• 通讯作者: et al.

Gemcitabine enhances Wilms’ tumor gene WT1 expression and sensitizes human pancreatic cancer cells with WT1-specific T-cell-mediated antitumor immune response

• DOI: 10.1007/s00262-011-1033-3
• 发表时间: 2011-05
• 期刊: Cancer Immunology, Immunotherapy
• 作者: Akitaka Takahara;S. Koido;Masaki Ito;Eijiro Nagasaki;Yukiko Sagawa;T. Iwamoto;H. Komita;T. Ochi;H. Fujiwara;M. Yasukawa;J. Mineno;H. Shiku;S. Nishida;H. Sugiyama;H. Tajiri;S. Homma