Mammalian myeloid progenitor cell subsets
    1.
    发明授权
    Mammalian myeloid progenitor cell subsets 有权
    哺乳动物骨髓祖细胞亚群

    公开(公告)号:US07618654B2

    公开(公告)日:2009-11-17

    申请号:US11874841

    申请日:2007-10-18

    IPC分类号: A61K35/28 G01N33/53

    摘要: A substantially enriched mammalian hematopoietic cell subpopulation is provided, which is characterized by progenitor cell activity for myeloid lineages, but lacking the potential to differentiate into lymphoid lineages. This population is further divided into specific myeloid progenitor subsets, including a common myeloid progenitor cells (CMP), megakaryocyte/erythroid progenitor cells (MEP) and granulocyte/monocyte lineage progenitor (GMP). Methods are provided for the isolation and culture of these subpopulations. The CMP population gives rise to all myeloid lineages, and can give rise to the two additional and isolatable progenitor populations that are exclusively committed to either the erythroid/megakaryocytic or myelomonocytic lineages. Tηε χελλ ενιχημεντ μετηoδσ εμπλoψεαγεντσ τηατ σπεχαλλψεψoγνιζε Tηψ-1; ανδIΛ-7 Pα, in conjunction with other markers expressed on lineage committed cells. These cells give rise to a variety of myeloid cells, including megakaryocytes, granulocytes, dendritic cells and erythroid cells, as evidenced by their growth and differentiation in vitro and in vivo.

    摘要翻译: 提供了基本上富集的哺乳动物造血细胞亚群,其特征在于骨髓谱系的祖细胞活性,但缺乏分化成淋巴谱系的潜力。 该群体进一步分为特定的骨髓祖细胞亚群,包括常见的髓系祖细胞(CMP),巨核细胞/红细胞祖细胞(MEP)和粒细胞/单核细胞谱系祖细胞(GMP)。 提供了用于分离和培养这些亚群体的方法。 CMP群体产生所有骨髓谱系,并且可以产生专门致力于红细胞/巨核细胞或骨髓单核细胞谱系的两个另外的和可分离的祖细胞群体。 “=”2.46mm“wi =”1.78mm“file =”US07618654-20091117-P00001.TIF“alt =”自定义字符“img-content =”character“ img-format =“tif”/> iotachietamuepsilonnutau muepsilontauetaodeltasigma epsilonmupilambdaopsi epsilonalphagammaepsilonnutausigma tauetaalphatau sigmapiepsilonchialphalambdalambdapsi epsilonpsiogammanuiotazetaepsilon Tetapsi-1; alphanudeltaILambda-7 Palpha,与在谱系确定的细胞上表达的其他标志物结合。 这些细胞产生各种骨髓细胞,包括巨核细胞,粒细胞,树突状细胞和红细胞,其体外和体内的生长和分化证明。

    Enrichment for a thymocyte subset having progenitor cell activity using
c-kit as a selection marker
    3.
    发明授权
    Enrichment for a thymocyte subset having progenitor cell activity using c-kit as a selection marker 失效
    使用c-kit作为选择标记对具有祖细胞活性的胸腺细胞亚群的富集

    公开(公告)号:US5821108A

    公开(公告)日:1998-10-13

    申请号:US418534

    申请日:1995-04-07

    摘要: A subpopulation in the CD4.sup.+ 8.sup.+ (DP) thymic blast population is identified that is the precursor for thymic T cells. All such progenitors are c-kit.sup.+. The c-kit.sup.+ subset expresses lower levels of CD4 and CD8 than the large and small DP c-kit- cells. These DP.sup.int c-kit.sup.+ cells differentiate to thymic T cells rapidly on heterogenous thymic stromal cell cultures. Similar maturation takes place in vivo over 4 days. A method for isolating the cells which are c-kit.sup.+ and which express intermediate or low levels of CD4+/CD8+ is also disclosed.

    摘要翻译: 鉴定出CD4 + 8 +(DP)胸腺细胞群中的亚群是胸腺T细胞的前体。 所有这些祖细胞都是c-kit +。 c-kit +子集表达比大和小的DP c-kit-细胞更低水平的CD4和CD8。 这些DPint c-kit +细胞在异源胸腺基质细胞培养物上快速分化为胸腺T细胞。 类似的成熟在体内发生4天以上。 还公开了分离c-kit +并表达中等或低水平的CD4 + / CD8 +的细胞的方法。

    Method for treatment of blood tumor using anti-TIM-3 antibody
    4.
    发明授权
    Method for treatment of blood tumor using anti-TIM-3 antibody 有权
    使用抗TIM-3抗体治疗血液肿瘤的方法

    公开(公告)号:US08647623B2

    公开(公告)日:2014-02-11

    申请号:US13263434

    申请日:2010-04-09

    IPC分类号: A61K39/395

    摘要: Disclosed is a therapeutic method comprising administering a TIM-3 antibody to a subject who is suspected to be suffering from blood tumor and in whom TIM-3 has been expressed in a Lin(−)CD34(+)CD38(−) cell fraction of bone marrow or peripheral blood or a subject who has been received any treatment for blood tumor. Also disclosed is a composition for preventing or treating blood tumor, which comprises a TIM-3 antibody as an active ingredient. Conceived diseases include those diseases which can be treated through the binding or targeting of the TIM-3 antibody to blood tumor cells (AML cells, CML cells, MDS cells, ALL cells, CLL cells, multiple myeloma cells, etc.), helper T cell (e.g., Th1 cells, Th17 cells), and antigen-presenting cells (e.g., dendritic cells, monocytes, macrophages, and cells resembling to the aforementioned cells (hepatic stellate cells, osteoclasts, microglial cells, intraepidermal macrophages, dust cells (alveolar macrophages), etc)), all of which are capable of expressing TIM-3. The diseases for which the therapeutic use is to be examined include blood diseases in which the expression of TIM-3 is observed in bone marrow or peripheral blood, particularly blood tumor.

    摘要翻译: 公开了一种治疗方法,其包括对怀疑患有血液肿瘤的受试者施用TIM-3抗体,并且在其中已经表达TIM-3的Lin( - )CD34(+)CD38( - )细胞级分中 骨髓或外周血或受到血肿治疗的受试者。 还公开了用于预防或治疗血液肿瘤的组合物,其包含TIM-3抗体作为活性成分。 想象中的疾病包括可以通过TIM-3抗体对血液肿瘤细胞(AML细胞,CML细胞,MDS细胞,ALL细胞,CLL细胞,多发性骨髓瘤细胞等)的结合或靶向治疗的那些疾病,辅助T 细胞(例如,Th1细胞,Th17细胞)和抗原呈递细胞(例如,树突状细胞,单核细胞,巨噬细胞和类似于上述细胞的细胞(肝星状细胞,破骨细胞,小神经胶质细胞,表皮内巨噬细胞,尘埃细胞(肺泡 巨噬细胞)等)),所有这些都能表达TIM-3。 要检查治疗用途的疾病包括在骨髓或外周血,特别是血肿瘤中观察到TIM-3的表达的血液疾病。

    METHOD FOR TREATMENT OF BLOOD TUMOR USING ANTI-TIM-3 ANTIBODY
    6.
    发明申请
    METHOD FOR TREATMENT OF BLOOD TUMOR USING ANTI-TIM-3 ANTIBODY 有权
    使用抗TIM-3抗体治疗血液肿瘤的方法

    公开(公告)号:US20120100131A1

    公开(公告)日:2012-04-26

    申请号:US13263434

    申请日:2010-04-09

    IPC分类号: A61K39/395 A61P35/00

    摘要: Disclosed is a therapeutic method comprising administering a TIM-3 antibody to a subject who is suspected to be suffering from blood tumor and in whom TIM-3 has been expressed in a Lin(−)CD34(+)CD38(−) cell fraction of bone marrow or peripheral blood or a subject who has been received any treatment for blood tumor. Also disclosed is a composition for preventing or treating blood tumor, which comprises a TIM-3 antibody as an active ingredient. Conceived diseases include those diseases which can be treated through the binding or targeting of the TIM-3 antibody to blood tumor cells (AML cells, CML cells, MDS cells, ALL cells, CLL cells, multiple myeloma cells, etc.), helper T cell (e.g., Th1 cells, Th17 cells), and antigen-presenting cells (e.g., dendritic cells, monocytes, macrophages, and cells resembling to the aforementioned cells (hepatic stellate cells, osteoclasts, microglial cells, intraepidermal macrophages, dust cells (alveolar macrophages), etc)), all of which are capable of expressing TIM-3. The diseases for which the therapeutic use is to be examined include blood diseases in which the expression of TIM-3 is observed in bone marrow or peripheral blood, particularly blood tumor.

    摘要翻译: 公开了一种治疗方法,其包括对怀疑患有血液肿瘤的受试者施用TIM-3抗体,并且在其中已经表达TIM-3的Lin( - )CD34(+)CD38( - )细胞级分中 骨髓或外周血或受到血肿治疗的受试者。 还公开了用于预防或治疗血液肿瘤的组合物,其包含TIM-3抗体作为活性成分。 想象中的疾病包括可以通过TIM-3抗体对血液肿瘤细胞(AML细胞,CML细胞,MDS细胞,ALL细胞,CLL细胞,多发性骨髓瘤细胞等)的结合或靶向治疗的那些疾病,辅助T 细胞(例如,Th1细胞,Th17细胞)和抗原呈递细胞(例如,树突状细胞,单核细胞,巨噬细胞和类似于上述细胞的细胞(肝星状细胞,破骨细胞,小神经胶质细胞,表皮内巨噬细胞,尘埃细胞(肺泡 巨噬细胞)等)),所有这些都能表达TIM-3。 要检查治疗用途的疾病包括在骨髓或外周血,特别是血肿瘤中观察到TIM-3的表达的血液疾病。

    Mammalian common lymphoid progenitor cell
    7.
    发明授权
    Mammalian common lymphoid progenitor cell 有权
    哺乳动物常见淋巴祖细胞

    公开(公告)号:US07297329B2

    公开(公告)日:2007-11-20

    申请号:US11093951

    申请日:2005-03-29

    IPC分类号: A01N65/00

    摘要: A substantially enriched mammalian hematopoietic cell subpopulation is provided, which is characterized by progenitor cell activity for lymphoid lineages, but lacking the potential to differentiate into myeloid and erythroid lineages. Methods are provided for the isolation and culture of this common lymphoid progenitor cell (CLP). The cell enrichment methods employ reagents that specifically recognize CDw127 (IL-7 receptor α); CD117 (c-kit) protein, in conjunction with other markers expressed on lineage committed cells. The murine cells are also characterized as expressing low levels of sca-1 (Ly-6E and Ly-6A). The CLPs are predominantly cycling, blast cells. These cells give rise to B cells, T cells and natural killer cells, as evidenced by their growth and differentiation in vitro and in vivo.

    摘要翻译: 提供了基本上富集的哺乳动物造血细胞亚群,其特征在于淋巴谱系的祖细胞活性,但缺乏分化为骨髓和红系谱系的潜力。 提供了用于分离和培养这种常见淋巴祖细胞(CLP)的方法。 细胞富集方法使用特异性识别CDw127(IL-7受体α)的试剂; CD117(c-kit)蛋白,与在谱系确定细胞上表达的其他标志物结合。 鼠细胞也被表征为表达低水平的sca-1(Ly-6E和Ly-6A)。 CLP主要是循环,胚细胞。 这些细胞产生B细胞,T细胞和自然杀伤细胞,这通过其体外和体内的生长和分化证明。

    MAMMALIAN MYELOID PROGENITOR CELL SUBSETS

    公开(公告)号:US20080131408A1

    公开(公告)日:2008-06-05

    申请号:US11874841

    申请日:2007-10-18

    IPC分类号: A01N63/00 C12N5/00

    摘要: A substantially enriched mammalian hematopoietic cell subpopulation is provided, which is characterized by progenitor cell activity for myeloid lineages, but lacking the potential to differentiate into lymphoid lineages. This population is further divided into specific myeloid progenitor subsets, including a common myeloid progenitor cells (CMP), megakaryocyte/erythroid progenitor cells (MEP) and granulocyte/monocyte lineage progenitor (GMP). Methods are provided for the isolation and culture of these subpopulations. The CMP population gives rise to all myeloid lineages, and can give rise to the two additional and isolatable progenitor populations that are exclusively committed to either the erythroid/megakaryocytic or myelomonocytic lineages. Tηε χελλ ενιχημεντ μετηoδσ εμπλoψεαγεντσ τηατ σπεχαλλψεψoγνιζε Tηψ-1; ανδIΛ-7 Pα, in conjunction with other markers expressed on lineage committed cells. These cells give rise to a variety of myeloid cells, including megakaryocytes, granulocytes, dendritic cells and erythroid cells, as evidenced by their growth and differentiation in vitro and in vivo.

    摘要翻译: 提供了基本上富集的哺乳动物造血细胞亚群,其特征在于骨髓谱系的祖细胞活性,但缺乏分化成淋巴谱系的潜力。 该群体进一步分为特定的骨髓祖细胞亚群,包括常见的髓系祖细胞(CMP),巨核细胞/红细胞祖细胞(MEP)和粒细胞/单核细胞谱系祖细胞(GMP)。 提供了用于分离和培养这些亚群体的方法。 CMP群体产生所有骨髓谱系,并且可以产生专门致力于红细胞/巨核细胞或骨髓单核细胞谱系的两个另外的和可分离的祖细胞群体。 “=”2.46mm“wi =”1.78mm“file =”US20080131408A1-20080605-P00001.TIF“img-content =”character“img-format =”tif“=”CUSTOM-CHARACTER-00001“ “/> iotachietamuepsilonnutau muepsilontauetaodeltasigma epsilonmupilambdaopsi epsilonalphagammaepsilonnutphaigma tauetaalphatau sigmapiepsilonchialphalambdalambdapsi epsilonpsiogammanuiotazetaepsilon Tetapsi-1; alphanudeltaILambda-7 Palpha,与在谱系确定的细胞上表达的其他标志物结合。 这些细胞产生各种骨髓细胞,包括巨核细胞,粒细胞,树突状细胞和红细胞,其体外和体内的生长和分化证明。

    Mammalian myeloid progenitor cell subsets
    9.
    发明授权
    Mammalian myeloid progenitor cell subsets 有权
    哺乳动物骨髓祖细胞亚群

    公开(公告)号:US06465247B1

    公开(公告)日:2002-10-15

    申请号:US09607529

    申请日:2000-06-29

    IPC分类号: C12N506

    摘要: A substantially enriched mammalian hematopoietic cell subpopulation is provided, which is characterized by progenitor cell activity for myeloid lineages, but lacking the potential to differentiate into lymphoid lineages. This population is further divided into specific myeloid progenitor subsets, including a common myeloid progenitor cells (CMP), megakaryocyte/erythroid progenitor cells (MEP) and granulocyte/monocyte lineage progenitor (GMP). Methods are provided for the isolation and culture of these subpopulations. The CMP population gives rise to all myeloid lineages, and can give rise to the two additional and isolatable progenitor populations that are exclusively committed to either the erythroid/megakaryocytic or myelomonocytic lineages. The cell enrichment methods employ reagents that specifically recognize CDw127 (IL-7 receptor &agr;); CD117 (c-kit) protein, in conjunction with other markers expressed on lineage committed cells. These cells give rise to a variety of myeloid cells, including megakaryocytes, granulocytes, dendritic cells and erythroid cells, as evidenced by their growth and differentiation in vitro and in vivo.

    摘要翻译: 提供了基本上富集的哺乳动物造血细胞亚群,其特征在于骨髓谱系的祖细胞活性,但缺乏分化成淋巴谱系的潜力。 该群体进一步分为特定的骨髓祖细胞亚群,包括常见的髓系祖细胞(CMP),巨核细胞/红细胞祖细胞(MEP)和粒细胞/单核细胞谱系祖细胞(GMP)。 提供了用于分离和培养这些亚群体的方法。 CMP群体产生所有骨髓谱系,并且可以产生专门致力于红细胞/巨核细胞或骨髓单核细胞谱系的两个另外的和可分离的祖细胞群体。 细胞富集方法使用特异性识别CDw127(IL-7受体α)的试剂; CD117(c-kit)蛋白,与在谱系确定细胞上表达的其他标志物结合。 这些细胞产生各种骨髓细胞,包括巨核细胞,粒细胞,树突状细胞和红细胞,其体外和体内的生长和分化证明。

    ANTI-TIM-3 ANTIBODY
    10.
    发明申请
    ANTI-TIM-3 ANTIBODY 有权
    抗TIM-3抗体

    公开(公告)号:US20120189617A1

    公开(公告)日:2012-07-26

    申请号:US13158622

    申请日:2011-06-13

    摘要: The present invention provides an anti-human TIM-3 antibody which binds to the amino acid sequence of the extracellular region of TIM-3 or its three-dimensional structure thereof and exhibits higher effector activity such as an antibody-dependent cellular cytotoxicity (ADCC activity) for diseases relating to a human TIM-3 expressing cell. The present invention provides a monoclonal antibody or antibody fragment thereof which binds to the amino acid sequence of the extracellular region of TIM-3 or its three-dimensional structure and exhibits ADCC activity; a hybridoma which produces the antibody; a DNA encoding the antibody; a vector comprising the DNA; a transformant which is obtainable by introducing the vector; a method for producing the antibody or the antibody fragment thereof which comprises using the hybridoma or the transformant; a therapeutic agent and a diagnostic agent comprising the antibody or the antibody fragment thereof as an active ingredient. In addition, the present invention provides an anti-human TIM-3 antibody having high ADCC activity by screening an anti-human TIM-3 antibody which competes with the monoclonal antibody or the antibody fragment thereof.

    摘要翻译: 本发明提供了结合TIM-3细胞外区域的氨基酸序列或其三维结构的抗人TIM-3抗体,并表现出更高的效应子活性,例如抗体依赖性细胞毒性(ADCC活性 )用于与TIM-3表达细胞相关的疾病。 本发明提供了结合TIM-3细胞外区域的氨基酸序列或其三维结构并表现出ADCC活性的单克隆抗体或其抗体片段; 产生抗体的杂交瘤; 编码抗体的DNA; 包含DNA的载体; 通过引入载体可获得的转化体; 包括使用该杂交瘤或转化体的抗体或其抗体片段的制备方法; 包含抗体或其抗体片段的治疗剂和诊断剂作为活性成分。 此外,本发明通过筛选与单克隆抗体或其抗体片段竞争的抗人TIM-3抗体,提供具有高ADCC活性的抗人TIM-3抗体。