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    Isolation and expression of a disabled protein gene mDab1 and methods
    72.
    发明授权
    Isolation and expression of a disabled protein gene mDab1 and methods 有权
    残留蛋白基因mDab1的分离和表达及方法

    公开(公告)号：US07250505B1

    公开(公告)日：2007-07-31

    申请号：US09486293

    申请日：1998-08-21

    申请人： Jonathan A. Cooper ,  Brian W. Howell

    发明人： Jonathan A. Cooper ,  Brian W. Howell

    IPC分类号： C12N15/09 ,  C07K14/47 ,  A61K39/395

    CPC分类号： C07K16/18 ,  C07K14/47

    摘要： A mammalian homology of Drosophila Disabled protein has been identified and cloned. In particular, the murine homolog designated mDab1 has been cloned and expressed. mDab1, when tyrosine phosphorylated, binds to the SH2 domain of Src, Abl and Fyn. Antibodies specific for mDab1 are provided as are methods for the screening of agents for their ability to modulate mDab1 activity. Methods for diagnosing Disabled protein associated disease are also provided.

    摘要翻译： 已经鉴定并克隆了果蝇残留蛋白的哺乳动物同源性。 特别地，已经克隆并表达了命名为mDab1的鼠同系物。 当酪氨酸磷酸化时，mDab1与Src，Abl和Fyn的SH2结构域结合。 提供了对于mDab1特异性的抗体，以及用于筛选试剂调节mDab1活性的能力的方法。 还提供了诊断残疾蛋白相关疾病的方法。

    Inhibition of lymphocyte adherence with CS-1-peptides and fragments thereof
    73.
    发明授权
    Inhibition of lymphocyte adherence with CS-1-peptides and fragments thereof 失效
    用CS-1肽及其片段抑制淋巴细胞粘附

    公开(公告)号：US07238668B1

    公开(公告)日：2007-07-03

    申请号：US08452098

    申请日：1995-05-26

    申请人： Elizabeth A. Wayner

    发明人： Elizabeth A. Wayner

    IPC分类号： A61K38/00 ,  A07K7/00

    CPC分类号： A61K38/39 ,  C07K14/7055 ,  C07K14/78 ,  C07K16/2842

    摘要： The present invention relates to a method for inhibiting the adhesion of one cell to another comprising interfering with the interaction between the extracellular matrix receptor and its ligand.The invention is based upon the discovery that the α4β1 extracellular matrix receptor promotes adhesion of lymphocytes to endothelial cells via attachment to a defined peptide sequence. Prior to the present invention, the ligand of the α4β1 receptor had not been identified, nor had the function of the α4β1 receptor in lymphocyte attachment been known. By preventing the interaction between the α4β1 receptor and its ligands using antibodies or defined peptide sequences, the present invention enables, for the first time, specific intervention in the migration of lymphocytes through the vascular endothelium and into tissues. The present invention, therefore, has particular clinical utility in suppression of the immune response; in various specific embodiments of the invention, the adherence of lymphocytes to endothelium may be inhibited systemically, or may, alternatively, be localized to particular tissues or circumscribed areas. Accordingly, the present invention provides for treatment of diseases involving autoimmune responses as well as other chronic or relapsing activations of the immune system, including allergy, asthma, and chronic inflammatory skin conditions.

    摘要翻译： 本发明涉及一种抑制一种细胞与另一种细胞粘附的方法，包括干扰细胞外基质受体及其配体之间的相互作用。 本发明基于以下发现：α4β1细胞外基质受体通过连接到限定的肽序列促进淋巴细胞粘附于内皮细胞。 在本发明之前，尚未鉴定出α4β1受体的配体，也没有已知淋巴细胞附着中α4β1受体的功能。 通过使用抗体或定义的肽序列防止α4β1受体及其配体之间的相互作用，本发明首次能够特异性介入淋巴细胞通过血管内皮和组织的迁移。 因此，本发明在抑制免疫应答方面具有特殊的临床效用; 在本发明的各种具体实施方案中，淋巴细胞对内皮的粘附可以全身抑制，或可替代地定位于特定组织或外切区域。 因此，本发明提供治疗涉及自身免疫反应以及免疫系统的其它慢性或复发性激活的疾病，包括过敏，哮喘和慢性炎性皮肤病症。

    Jaagsiekte sheep retroviral packaging cell lines and methods relating thereto
    75.
    发明申请
    Jaagsiekte sheep retroviral packaging cell lines and methods relating thereto 审中-公开
    Jaagsiekte绵羊逆转录病毒包装细胞系及其相关方法

    公开(公告)号：US20030104357A1

    公开(公告)日：2003-06-05

    申请号：US10112178

    申请日：2002-03-29

    申请人： Fred Hutchinson Cancer Research Center

    发明人： Sharath K. Rai ,  Arthur Dusty Miller

    IPC分类号： C12Q001/70 ,  C12P021/06 ,  C12P019/34 ,  A61K039/12 ,  A61K039/21

    CPC分类号： C12N7/00 ,  C12N2740/10052

    摘要： The present invention demonstrates that JSRV envelope protein (Env) can be used to transduce human and other mammalian cells. Hybrid retrovirus packaging cells have been constructed that express the JSRV Env and retrovirus Gag-Pol proteins, and can produce JSRV-pseudotype vectors at high titers. Using high-titer virus the host range for JSRV has been established, and included sheep, human, monkey, bovine and dog cells, but not murine, rat or hamster cells. Retroviral packaging cell lines comprising the JSRV envelope protein, and receptor binding fragments thereof, are provided which transiently and stably produce high titers of recombinant retrovirus particles which can be used to transfer a heterologous gene to a eukaryotic cell.

    摘要翻译： 本发明证明JSRV包膜蛋白（Env）可用于转导人和其他哺乳动物细胞。 已经构建了表达JSRV Env和逆转录病毒Gag-Pol蛋白的混合逆转录病毒包装细胞，并且可以以高效价产生JSRV-假型载体。 使用高滴度病毒，建立了JSRV的宿主范围，包括羊，人，猴，牛和狗细胞，但不包括鼠，大鼠或仓鼠细胞。 提供了包含JSRV包膜蛋白的逆转录病毒包装细胞系及其受体结合片段，其瞬时稳定地产生可用于将异源基因转移到真核细胞的高滴度重组逆转录病毒颗粒。

    "> High efficiency transduction of T lymphocytes using rapid expansion methods (
    76.
    发明授权
    High efficiency transduction of T lymphocytes using rapid expansion methods ("REM") 失效
    使用快速扩增方法（“REM”）高效转导T淋巴细胞

    公开(公告)号：US06040177A

    公开(公告)日：2000-03-21

    申请号：US614585

    申请日：1996-03-13

    申请人： Stanley R. Riddell ,  Philip D. Greenberg

    发明人： Stanley R. Riddell ,  Philip D. Greenberg

    IPC分类号： C12N15/09 ,  A61K35/14 ,  A61K39/00 ,  C12N5/02 ,  C12N5/0783 ,  C12N5/10 ,  C12N15/11 ,  C07K14/55 ,  C07K16/28

    CPC分类号： C12N5/0636 ,  A61K2039/5158 ,  C12N2501/23 ,  C12N2501/515 ,  C12N2502/11 ,  C12N2510/00 ,  C12N2799/027

    摘要： The present invention provides a rapid expansion method (termed "REM"), for quickly generating large numbers of T lymphocytes, including cytolytic and helper T lymphocytes. REM involves culturing the T cells in association with a disproportionately large concentration of nondividing feeder cells, preferably .gamma.-irradiated peripheral blood mononuclear cells ("PBMC") present at an excess of at least 40-fold (relative to the number of target T cells), more preferably at an excess of at least about 200-fold. Cultures grown under REM exhibit dramatically enhanced expansion rates that can be even further elevated by the use of appropriate concentrations of an additional feeder cell, an anti-CD3 monoclonal antibody and IL-2, as described herein. Clonal expansions in the range of 500-fold to 3000-fold can be achieved within a single stimulation cycle of about 10-13 days, which is more than 100-fold more efficient than currently employed methods of culturing human T cell clones. Genetic transduction efficiencies were also enhanced using REM-expanded T lymphocytes. Several examples involving human bone marrow transplant recipients illustrate the effective use of REM-expanded antigen-specific cytotoxic T lymphocytes for adoptive immunotherapy in humans.

    摘要翻译： 本发明提供了快速产生大量T淋巴细胞（包括溶细胞和辅助性T淋巴细胞）的快速扩增方法（称为“REM”）。 REM涉及培养T细胞与不相称大浓度的非分裂饲养细胞，优选以超过至少40倍（相对于靶T细胞数目）存在的γ-照射的外周血单核细胞（“PBMC”） ），更优选超过至少约200倍。 在REM下生长的培养物显示出显着增强的扩增速率，通过使用适当浓度的另外的饲养细胞，抗CD3单克隆抗体和IL-2，如本文所述，其可进一步提高。 可以在约10-13天的单个刺激周期内实现500倍至3000倍范围内的克隆扩增，其比目前使用的培养人T细胞克隆的方法高出100倍。 使用REM扩增的T淋巴细胞，遗传转导效率也得到提高。 涉及人骨髓移植受体的几个实例说明了REM扩增的抗原特异性细胞毒性T淋巴细胞在人类中的过继性免疫治疗的有效用途。

    "> Rapid expansion method (
    77.
    发明授权
    Rapid expansion method ("REM") for in vitro propagation of T lymphocytes 失效
    用于T淋巴细胞体外繁殖的快速扩增方法（“REM”）

    公开(公告)号：US5827642A

    公开(公告)日：1998-10-27

    申请号：US317100

    申请日：1994-10-03

    申请人： Stanley R. Riddell ,  Philip D. Greenberg

    发明人： Stanley R. Riddell ,  Philip D. Greenberg

    IPC分类号： C12N15/09 ,  A61K35/14 ,  A61K39/00 ,  C12N5/02 ,  C12N5/0783 ,  C12N5/10 ,  C12N5/08 ,  A01N1/02 ,  A61K35/12

    CPC分类号： C12N5/0636 ,  A61K2039/5158 ,  C12N2501/23 ,  C12N2501/515 ,  C12N2502/11 ,  C12N2510/00 ,  C12N2799/027

    摘要： The present invention provides a rapid expansion method (termed "REM"), for quickly generating large numbers of T lymphocytes, including cytolytic and helper T lymphocytes. REM involves culturing the T cells in association with a disproportionately large concentration of nondividing feeder cells, preferably .gamma.-irradiated peripheral blood mononuclear cells ("PBMC") present at an excess of at least 40-fold (relative to the number of target T cells), more preferably at an excess of at least about 200-fold. Cultures grown under REM exhibit dramatically enhanced expansion rates that can be even further elevated by the use of appropriate concentrations of an additional feeder cell, an anti-CD3 monoclonal antibody and IL-2, as described herein. Clonal expansions in the range of 500-fold to 3000-fold can be achieved within a single stimulation cycle of about 10-13 days, which is more than 100-fold more efficient than currently employed methods of culturing human T cell clones. Genetic transduction efficiencies were also enhanced using REM-expanded T lymphocytes. Several examples involving human bone marrow transplant recipients illustrate the effective use of REM-expanded antigen-specific cytotoxic T lymphocytes for adoptive immunotherapy in humans.

    摘要翻译： 本发明提供了快速产生大量T淋巴细胞（包括溶细胞和辅助性T淋巴细胞）的快速扩增方法（称为“REM”）。 REM涉及培养T细胞与不相称大浓度的非分裂饲养细胞，优选以超过至少40倍（相对于靶T细胞数目）存在的γ-照射的外周血单核细胞（“PBMC”） ），更优选超过至少约200倍。 在REM下生长的培养物显示出显着增强的扩增速率，通过使用适当浓度的另外的饲养细胞，抗CD3单克隆抗体和IL-2，如本文所述，其可进一步提高。 可以在约10-13天的单个刺激周期内实现500倍至3000倍范围内的克隆扩增，其比目前使用的培养人T细胞克隆的方法高出100倍。 使用REM扩增的T淋巴细胞，遗传转导效率也得到提高。 涉及人骨髓移植受体的几个实例说明了REM扩增的抗原特异性细胞毒性T淋巴细胞在人类中的过继性免疫治疗的有效用途。