Development of cancer immunotherapy using co-transfer of cancer-specific TCR gene and chemokine receptor gene

利用癌症特异性TCR基因和趋化因子受体基因共转移开发癌症免疫疗法

• 批准号: 21390294
• 负责人: YASUKAWA Masaki
• 金额: $ 11.48万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390294/
• 关键词: がん免疫療法; T細胞レセプター遺伝子; ケモカイン・ケモカインレセプター; WT1; Aurora-A kinase; 白血病; 肺がん; WTI; 遺伝子治療; 細胞傷害性T細胞; T細胞レセプター; ケモカイン; ヒト化マウス; がん免疫; レトロウイルスベクター

In order to develop a novel cancer immunotherapy, we verified the efficacy and safety of adoptive transfer using cytotoxic T lymphocytes(CTLs) transduced with cancer-specific T-cell receptor(TCR) gene and receptor gene for chemokine which is abundantly produced in cancer microenvironment. Our data demonstrate that adoptive transfer of artificial CTLs expressing both cancer-specific TCR and chemokine receptor is more effective and safe than that of CTLs expressing only cancer-specific TCR.

为了开发一种新的肿瘤免疫治疗方法，我们验证了转导肿瘤特异性T细胞受体(TCR)基因和肿瘤微环境中大量产生的趋化因子受体基因的细胞毒性T淋巴细胞(CTL)过继转移的有效性和安全性。我们的数据表明，过继转移同时表达肿瘤特异性TCR和趋化因子受体的人工CTL比只表达肿瘤特异性TCR的CTL更有效和安全。

项目成果

Generation of functional human T cells with HLA-restricted immune responses in HLA-class I expressing NOD/SCID/IL2rγ^<null> humanized mice

在表达 HLA-I 类 NOD/SCID/IL2rγ^<null> 人源化小鼠中产生具有 HLA 限制性免疫反应的功能性人类 T 细胞

• 发表时间: 2010
• 期刊: Proc. Natl. Acad. Sci. USA
• 作者: Shultz;L.;Fujiwara;H.;Yasukawa;M.;他9名
• 通讯作者: 他9名

Relapse of renal cell carcinoma with disappearance of HLA class I following hTERT peptide vaccination.

• DOI: 10.1093/annonc/mdq544
• 发表时间: 2010-10
• 期刊: Annals of oncology : official journal of the European Society for Medical Oncology
• 作者: M. Yasukawa;T. Ochi;H. Fujiwara

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

Forced Expression of CC Chemokine Receptor 2 Enhances Anti-Cancer Reactivity Mediated by T Lymphocytes Beforehand Redirected Toward WT1 Inside the Tumor Microenvironment

CC 趋化因子受体 2 的强制表达可增强肿瘤微环境中预先重定向至 WT1 的 T 淋巴细胞介导的抗癌反应性

• 发表时间: 2011
• 作者: Asai A;Yasukawa M;et al
• 通讯作者: et al

Peroxisome proliferator-activated receptorαandγagonists together with TGF-βconvert human CD4+ CD25-T cells into functional Foxp3+ regulatory T cells

过氧化物酶体增殖物激活受体α和γ激动剂与TGF-β一起将人CD4+ CD25-T细胞转化为功能性Foxp3+调节性T细胞

• 发表时间: 2010
• 作者: Hasegawa H;Lei J;Matsumoto T;Yasukawa M
• 通讯作者: Yasukawa M