Novel immunogene therapy for hematopoietic malignancies
造血系统恶性肿瘤的新型免疫基因疗法
基本信息
- 批准号:15390301
- 负责人:
- 金额:$ 9.41万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2003
- 资助国家:日本
- 起止时间:2003 至 2004
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We performed studies on immunogene therapy for hematopoietic malignanicies. The data obtained from the series of study are as follows. 1) Myeloma cells are sensitive to perforin-dependent cytotoxicity mediated by WT1-specifici cytotoxic T lymphocytes (CTLs). 2)There is a difference in the control of perforin expression between CD4^+ and CD8^+ CTLs ; that is, perforin is expressed constitutively in memory CD8^+ CTLs, but is dependent on cell activation in memory CD4^+ CTLs. 3)T-cell receptor (TCR) α and β genes obtained from an HLA-A24-restricted, WT1 peptide-specific CTL clone were lentivirally transduced to polyclonally-activated T lymphocytes. TCR gene-transduced CD4+ and CD8+ T lymphocytes showed HLA-A24-restricted and WT1-specific reactivity against leukemia cells. 4)The WT1-derived epitope recognized by HLA-DP5-restricted CD4+ T-cell clone was identified. WT1-specific CD4+ T-cell clone exerted the perforin-dependent cytotoxicity against leukemia cells. 5)Phase I clinical study of cancer peptide vaccine using WT1-derived and hTERT-derived peptides has been continued. 6) Human immune system was constructed in the novel immundeficient mice by transplantation of human hematopoietic stem cells.
我们对造血系统恶性肿瘤的免疫基因治疗进行了研究。从该系列研究中获得的数据如下。1)骨髓瘤细胞对WT 1特异性细胞毒性T淋巴细胞(CTL)介导的穿孔素依赖性细胞毒性敏感。2)CD 4 ^+和CD 8 ^+ CTL对穿孔素表达的控制存在差异;也就是说,穿孔素在记忆性CD 8 ^+ CTL中组成型表达,但在记忆性CD 4 ^+ CTL中依赖于细胞活化。3)将从HLA-A24限制性、WT 1肽特异性CTL克隆获得的T细胞受体(TCR)α和β基因用慢病毒转导至多克隆活化的T淋巴细胞。TCR基因转导的CD 4+和CD 8 + T淋巴细胞对白血病细胞表现出HLA-A24限制性和WT 1特异性反应。4)鉴定了HLA-DP 5限制性CD 4 + T细胞克隆识别的WT 1衍生表位。WT 1特异性CD 4 + T细胞克隆对白血病细胞具有穿孔素依赖的细胞毒作用。5)使用WT 1衍生肽和hTERT衍生肽的癌肽疫苗的I期临床研究一直在继续。6)通过移植人造血干细胞在新型免疫缺陷小鼠中构建人免疫系统。
项目成果
期刊论文数量(40)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Generation of human tumor-specific, HLA class I-restricted Th1 and Tc1 cells by cell engineering with tumor peptide-specific T cell receptor genes.
通过使用肿瘤肽特异性 T 细胞受体基因进行细胞工程,生成人类肿瘤特异性、HLA I 类限制性 Th1 和 Tc1 细胞。
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:Tsuji T;Yasukawa M;Matsuzaki J;Ohkuri T;Chamoto K;Wakita D;Azuma T;Niiya H;Miyoshi H;Kuzushima K;Oka Y;Sugiyama H;Ikeda H;Nishimura T.
- 通讯作者:Nishimura T.
Yanai, F., Yasukawa, M., et al.: "Essential roles of perforin in antigen-specific cytotoxicity mediated by human CD4^+ T lymphocytes : analysis using the combination of hereditary perforin-deficient effector cells and fas-deficient target cells"J.Immunol.
Yanai, F., Yasukawa, M., et al.:“穿孔素在人 CD4^ T 淋巴细胞介导的抗原特异性细胞毒性中的重要作用:使用遗传性穿孔素缺陷效应细胞和 fas 缺陷靶细胞的组合进行分析”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Identification of novel MUNC13-4 mutations in familial hemophagocytic lymphohistiocytosis and functional analysis of MUNC 13-4-deficient cytotoxic T lymphocytes.
家族性噬血细胞性淋巴组织细胞增多症中新型 MUNC13-4 突变的鉴定以及 MUNC 13-4 缺陷型细胞毒性 T 淋巴细胞的功能分析。
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Yamamoto;K.;Ishii;E.;Sako;M.;Ohga;S.;Furuno;K.;Suzuki;N.;Ueda;I.;Imayoshi;M.;Yamamoto;S.;Morimoto;A.;Takada;H.;Hara;T.;Imashuku;S.;Sasazuki;T.;Yasukawa;M.
- 通讯作者:M.
Essential roles of perforin in antigen-specific cytotoxicity mediated by human CD4[+] T lymphocytes : analysis using the combination of hereditary perforin-deficient effector cells and Fas-deficient target cells
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:柳井 文男
- 通讯作者:柳井 文男
Human cord blood- and bone marrow-derived CD34+ cells regenerate gastrointestinal epithelial cells
- DOI:10.1096/fj.04-2396fje
- 发表时间:2004-10-01
- 期刊:
- 影响因子:4.8
- 作者:Ishikawa, F;Yasukawa, M;Harada, M
- 通讯作者:Harada, M
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YASUKAWA Masaki其他文献
Menin plays an critical role in the survival of antigen-specific activated CD8+ T cells
Menin 在抗原特异性激活的 CD8 T 细胞的存活中发挥着关键作用
- DOI:
- 发表时间:
2015 - 期刊:
- 影响因子:0
- 作者:
YAMADA Takeshi;KANOH Makoto;MATSUMOTO Akira;YASUOKA Toshiaki;SUZUKI Junpei;MARUYAMA Saho;KUWAHARA Makoto;YASUKAWA Masaki;YAMASHITA Masakatsu - 通讯作者:
YAMASHITA Masakatsu
A tumor suppressor Menin controls CD8 T cell senescence by regulating glutamine metabolism
肿瘤抑制因子 Menin 通过调节谷氨酰胺代谢来控制 CD8 T 细胞衰老
- DOI:
- 发表时间:
2016 - 期刊:
- 影响因子:0
- 作者:
SUZUKI Junpei;KUWAHARA;Makoto;YASUKAWA Masaki;YAMASHITA Masakatsu - 通讯作者:
YAMASHITA Masakatsu
The tumor suppressor menin epigenetically regulates CD8 T cell senescence via the modulation of glutamine metabolism
肿瘤抑制蛋白 menin 通过调节谷氨酰胺代谢从表观遗传学角度调节 CD8 T 细胞衰老
- DOI:
- 发表时间:
2017 - 期刊:
- 影响因子:0
- 作者:
SUZUKI Junpei;KUWAHARA Makoto;YAMADA Takeshi;YASUKAWA Masaki;YAMASHITA Masakatsu - 通讯作者:
YAMASHITA Masakatsu
YASUKAWA Masaki的其他文献
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{{ truncateString('YASUKAWA Masaki', 18)}}的其他基金
Development of the novel gene-immunotherapy using artificial CTL targeting leukemia stem cells
使用人工CTL靶向白血病干细胞开发新型基因免疫疗法
- 批准号:
24390245 - 财政年份:2012
- 资助金额:
$ 9.41万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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 - 财政年份:2011
- 资助金额:
$ 9.41万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
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 - 财政年份:2009
- 资助金额:
$ 9.41万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Novel hematopoietic stem cell transplantation using cancer-specific T-cell receptor gene transfer
使用癌症特异性 T 细胞受体基因转移的新型造血干细胞移植
- 批准号:
19390265 - 财政年份:2007
- 资助金额:
$ 9.41万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of novel immunogene therapy for hamatopietic malignancies
造血系统恶性肿瘤新型免疫基因疗法的开发
- 批准号:
17390278 - 财政年份:2005
- 资助金额:
$ 9.41万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Identification of novel cancer-specific antigens and application for cellular imunotherapy of hematological malignancies
新型癌症特异性抗原的鉴定及其在血液恶性肿瘤细胞免疫治疗中的应用
- 批准号:
13470206 - 财政年份:2001
- 资助金额:
$ 9.41万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of novel immunogene therapy for hematological malignancies
血液系统恶性肿瘤新型免疫基因疗法的开发
- 批准号:
12557081 - 财政年份:2000
- 资助金额:
$ 9.41万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Immunogene therapy of cancer and virus infections using immortalized T-cell clones
使用永生化 T 细胞克隆对癌症和病毒感染进行免疫基因治疗
- 批准号:
11670449 - 财政年份:1999
- 资助金额:
$ 9.41万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular analysis of new herpesvirusinfections
新疱疹病毒感染的分子分析
- 批准号:
09670477 - 财政年份:1997
- 资助金额:
$ 9.41万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Abnormality of signal Transduction via T-cell receptors mediated by retrovirus infection
逆转录病毒感染介导的T细胞受体信号转导异常
- 批准号:
02670283 - 财政年份:1990
- 资助金额:
$ 9.41万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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