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    Nucleic acids encoding CD100 molecules
    1.
    发明授权
    Nucleic acids encoding CD100 molecules 失效
    编码CD100分子的核酸

    公开(公告)号：US07700102B2

    公开(公告)日：2010-04-20

    申请号：US10320769

    申请日：2002-12-16

    申请人： Kathryn T. Hall ,  Gordon J. Freeman ,  Joachim L. Schultze ,  Vassiliki A. Boussiotis ,  Lee M. Nadler ,  Laurence Boumsell ,  Armand Bensussan

    发明人： Kathryn T. Hall ,  Gordon J. Freeman ,  Joachim L. Schultze ,  Vassiliki A. Boussiotis ,  Lee M. Nadler ,  Laurence Boumsell ,  Armand Bensussan

    IPC分类号： A61K39/395

    CPC分类号： C07K14/70503 ,  A61K38/00 ,  C07K14/70575 ,  C07K16/2803 ,  C07K2319/00

    摘要： Isolated nucleic acid molecules encoding novel CD100 molecules which stimulate a leukocyte response, such as a B cell response, including B cell aggregation, B cell differentiation, B cell survival, and/or T cell proliferation are disclosed. These novel molecules have a certain homology to semaphorins, proteins which are growth cone guidance molecules that are critical for guiding growing axons of neurons to their targets. In addition to isolated nucleic acids molecules, antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced are also described. The invention further provides isolated CD100 proteins, fusion proteins and active fragments thereof. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

    摘要翻译： 公开了编码新的CD100分子的分离的核酸分子，其刺激白细胞应答，例如B细胞应答，包括B细胞聚集，B细胞分化，B细胞存活和/或T细胞增殖。 这些新型分子与semaphorins具有一定的同源性，蛋白质是生长锥形引导分子，对于将神经元的生长轴突引导到其靶点至关重要。 还描述了分离的核酸分子，含有本发明的核酸分子的重组表达载体的反义核酸分子，已经引入了表达载体的宿主细胞。 本发明还提供了分离的CD100蛋白，融合蛋白及其活性片段。 还提供了利用本发明组合物的诊断和治疗方法。

    CD100 antigen and uses therefor
    2.
    发明授权
    CD100 antigen and uses therefor 失效
    CD100抗原，并用于此

    公开(公告)号：US06576754B2

    公开(公告)日：2003-06-10

    申请号：US08556422

    申请日：1995-11-09

    申请人： Kathryn T. Hall ,  Gordon J. Freeman ,  Joachim L. Schultze ,  Vassiliki A. Boussiotis ,  Lee M. Nadler

    发明人： Kathryn T. Hall ,  Gordon J. Freeman ,  Joachim L. Schultze ,  Vassiliki A. Boussiotis ,  Lee M. Nadler

    IPC分类号： C07H2104

    CPC分类号： C07K14/70503 ,  A61K38/00 ,  C07K14/70575 ,  C07K16/2803 ,  C07K2319/00

    摘要： Isolated nucleic acid molecules encoding novel CD100 molecules which stimulate a leukocyte response, such as a B cell response, including B cell aggregation, B cell differentiation, B cell survival, and/or T cell proliferation are disclosed. These novel molecules have a certain homology to semaphorins, proteins which are growth cone guidance molecules that are critical for guiding growing axons of neurons to their targets. In addition to isolated nucleic acids molecules, antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced are also described. The invention further provides isolated CD100 proteins, fusion proteins and active fragments thereof. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

    摘要翻译： 公开了编码新的CD100分子的分离的核酸分子，其刺激白细胞应答，例如B细胞应答，包括B细胞聚集，B细胞分化，B细胞存活和/或T细胞增殖。 这些新型分子与semaphorins具有一定的同源性，蛋白质是生长锥形引导分子，对于将神经元的生长轴突引导到其靶点至关重要。 还描述了分离的核酸分子，含有本发明的核酸分子的重组表达载体的反义核酸分子，已经引入了表达载体的宿主细胞。 本发明还提供了分离的CD100蛋白，融合蛋白及其活性片段。 还提供了利用本发明组合物的诊断和治疗方法。

    Method of promoting b-cell proliferation and activation with CD40 ligand and cyclosporin
    4.
    发明授权
    Method of promoting b-cell proliferation and activation with CD40 ligand and cyclosporin 失效
    用CD40配体和环孢菌素促进b细胞增殖和活化的方法

    公开(公告)号：US06465251B1

    公开(公告)日：2002-10-15

    申请号：US08748341

    申请日：1996-11-13

    申请人： Joachim L. Schultze ,  Gordon J. Freeman ,  John G. Gribben ,  Lee M. Nadler

    发明人： Joachim L. Schultze ,  Gordon J. Freeman ,  John G. Gribben ,  Lee M. Nadler

    IPC分类号： C12N502

    CPC分类号： C12N5/0635 ,  C12N2501/04 ,  C12N2501/23 ,  C12N2501/52

    摘要： We teach a strategy to obtain large quantities of desired APCs, activated B cells, which are superior in their capacity to present tumor protein antigen in a multiadministration protocol. Human B cells can be obtained from peripheral blood in large numbers. These cells can be activated in vitro by coculture with CD40L (CD40-B cells) and an immunosuppressive agent such as cyclosporin A. They can expanded up to 1×103 to 1×104 fold in 2 weeks or 1×105 to 1×106 fold in 2 months. We demonstrate these cells are most efficient APCs comparable to DCs in stimulating allogeneic CD4+ CD45RA+, CD4+ CD45RO+, and CD8+ T cells. In contrast to DCs, CD40-B cells are fully functional even in the presence of immunosuppressive cytokines such as IL-10 and TGF&bgr;.

    摘要翻译： 我们教授一种策略，以获得大量所需的APC，活化的B细胞，其在多重给药方案中具有优于其呈递肿瘤蛋白抗原的能力。 人B细胞可以从外周血大量获得。 这些细胞可以通过与CD40L（CD40-B细胞）和免疫抑制剂如环孢菌素A的共培养在体外进行活化。它们可以在2周内扩增至1×10 3至1×10 4倍，在2个月内可扩增至1×10 5至1×10 6倍。 我们证明这些细胞是最有效的APC，与刺激同种异体CD4 + CD45RA +，CD4 + CD45RO +和CD8 + T细胞的DC相当。 与DC相反，即使在免疫抑制性细胞因子如IL-10和TGFbeta的存在下，CD40-B细胞也是完全功能的。

    Methods of inducing a T cell mediated immune response by administering antigen presenting B cells
    5.
    发明授权
    Methods of inducing a T cell mediated immune response by administering antigen presenting B cells 有权
    通过施用抗原呈递B细胞诱导T细胞介导的免疫应答的方法

    公开(公告)号：US07195758B2

    公开(公告)日：2007-03-27

    申请号：US10186416

    申请日：2002-07-01

    申请人： Joachim L. Schultze ,  Gordon J. Freeman ,  John G. Gribben ,  Lee M. Nadler

    发明人： Joachim L. Schultze ,  Gordon J. Freeman ,  John G. Gribben ,  Lee M. Nadler

    IPC分类号： A01N1/00 ,  A61K35/14 ,  A61K35/26

    CPC分类号： C12N5/0635 ,  C12N2501/04 ,  C12N2501/23 ,  C12N2501/52

    摘要： We teach a strategy to obtain large quantities of desired APCs, activated B cells, which are superior in their capacity to present tumor protein antigen in a multiadministration protocol. Human B cells can be obtained from peripheral blood in large numbers. These cells can be activated in vitro by coculture with CD40L (CD40-B cells) and an immunosuppressive agent such as cyclosporin A. They can expanded up to 1×103 to 1×104 fold in 2 weeks or 1×105 to 1×106 fold in 2 months. We demonstrate these cells are most efficient APCs comparable to DCs in stimulating allogeneic CD4+ CD45RA+, CD4+ CD45RO+, and CD8+ T cells. In contrast to DCs, CD40-B cells are fully functional even in the presence of immunosuppressive cytokines such as IL-10 and TGFβ.

    摘要翻译： 我们教授一种策略，以获得大量所需的APC，活化的B细胞，其在多重给药方案中具有优于其呈递肿瘤蛋白抗原的能力。 人B细胞可以从外周血大量获得。 这些细胞可以通过与CD40L（CD40-B细胞）和免疫抑制剂如环孢菌素A共培养在体外进行活化。它们可以扩增至1×10 3至1×10 4个/ 在2个月内为1倍或1×10 5至1×10 6倍。 我们证明这些细胞是最有效的APC，与刺激同种异体CD4 + CD45RA + +，+ CD4 + CD45RO + >和CD8 + T细胞。 与DC相反，即使在免疫抑制性细胞因子如IL-10和TGFbeta的存在下，CD40-B细胞也是完全功能的。

    Methods for stimulating T cell responses by manipulating a common cytokine receptor &ggr; chain
    6.
    发明授权
    Methods for stimulating T cell responses by manipulating a common cytokine receptor &ggr; chain 失效
    通过操纵常见的细胞因子受体γ链来刺激T细胞应答的方法

    公开(公告)号：US06576236B1

    公开(公告)日：2003-06-10

    申请号：US08270152

    申请日：1994-07-01

    申请人： Vassiliki A. Boussiotis ,  Lee M. Nadler

    发明人： Vassiliki A. Boussiotis ,  Lee M. Nadler

    IPC分类号： A61K39395

    CPC分类号： C07K14/715 ,  A61K38/2026 ,  A61K38/2046 ,  C07K16/244 ,  C07K16/2866 ,  G01N33/6869

    摘要： When stimulated through the T cell receptor(TCR)/CD3 complex without requisite costimulation through the CD28/B7 interaction, T cells enter a state of antigen specific unresponsiveness or anergy. This invention is based, at least in part, on the discovery that signaling though a common cytokine receptor &ggr; chain (e.g., interleukin-2 receptor, interleukin-4 receptor, interleukin-7 receptor) prevents the induction of T cell anergy. This &ggr; chain has been found to be associated with a JAK kinase having a molecular weight of about 116 kD (as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis) and signaling through the &ggr; chain induces phosphorylation of the JAK kinase. Accordingly, methods for stimulating or inhibiting proliferation by a T cell which expresses a cytokine receptor &ggr; chain are disclosed.

    摘要翻译： 当通过CD28 / B7相互作用刺激通过T细胞受体（TCR）/ CD3复合物而没有必要的共刺激时，T细胞进入抗原特异性无反应或无反应的状态。 本发明至少部分地基于以下发现，即通过常见的细胞因子受体γ链（例如白细胞介素-2受体，白细胞介素-4受体，白细胞介素-7受体）的信号传导阻止T细胞无反应的诱导。 已经发现该γ链与具有约116kD分子量（通过十二烷基硫酸钠聚丙烯酰胺凝胶电泳测定）的JAK激酶相关，并且通过γ链的信号传导诱导JAK激酶的磷酸化。 因此，公开了用于刺激或抑制表达细胞因子受体γ链的T细胞增殖的方法。

    B7-2: a CTLA4/CD28 ligand
    9.
    发明授权
    B7-2: a CTLA4/CD28 ligand 失效
    B7-2：CTLA4 / CD28配体

    公开(公告)号：US5942607A

    公开(公告)日：1999-08-24

    申请号：US101624

    申请日：1993-07-26

    申请人： Gordon J. Freeman ,  Lee M. Nadler ,  Gary S. Gray

    发明人： Gordon J. Freeman ,  Lee M. Nadler ,  Gary S. Gray

    IPC分类号： A61K38/00 ,  C07K14/705 ,  C07K16/28 ,  C12N15/12 ,  C12N15/85 ,  C07H21/00

    CPC分类号： C12N15/8509 ,  C07K14/70532 ,  C07K16/2827 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2267/03 ,  A01K2267/0381 ,  A61K38/00 ,  C07K2317/73 ,  C07K2319/30

    摘要： Isolated nucleic acids encoding novel CTLA4/CD28 ligands which costimulate T cell activation are disclosed. In one embodiment, the isolated nucleic acid has a sequence which encodes a B lymphocyte activation antigen, B7-2. Preferably, the nucleic acid is a DNA molecule comprising at least a portion of a nucleotide sequence shown in FIG. 8, SEQ ID NO: 1. The nucleic acid sequences of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also disclosed are host cells transformed to produce proteins or peptides encoded by the nucleic acid sequences of the invention and isolated proteins and peptides which comprise at least a portion of a novel B lymphocyte antigen.

    摘要翻译： 公开了分泌的编码新型CTLA4 / CD28配体的核酸，其共同刺激T细胞活化。 在一个实施方案中，分离的核酸具有编码B淋巴细胞活化抗原B7-2的序列。 优选地，核酸是包含图1所示的核苷酸序列的至少一部分的DNA分子。 8，SEQ ID NO：1。本发明的核酸序列可以整合到各种表达载体中，其又可以指导各种宿主，特别是真核细胞（例如哺乳动物和哺乳动物）中相应的蛋白质或肽的合成 昆虫细胞培养。 还公开了转化以产生由本发明的核酸序列编码的蛋白质或肽的宿主细胞和包含至少一部分新型B淋巴细胞抗原的分离的蛋白质和肽。

    Nucleic acid molecules encoding B7-1
    10.
    发明授权
    Nucleic acid molecules encoding B7-1 失效
    编码B7-1的核酸分子

    公开(公告)号：US07619078B2

    公开(公告)日：2009-11-17

    申请号：US11589275

    申请日：2006-10-26

    申请人： Arlene H. Sharpe ,  Francescopaolo Borriello ,  Gordon J. Freeman ,  Lee M. Nadler

    发明人： Arlene H. Sharpe ,  Francescopaolo Borriello ,  Gordon J. Freeman ,  Lee M. Nadler

    IPC分类号： C12N15/12 ,  C12N15/11 ,  C07K14/705

    CPC分类号： C07K14/70532 ,  A01K2217/05

    摘要： Novel structural forms of T cell costimulatory molecules are described. These structural forms comprise a novel structural domain or have a structural domain deleted or added. The structural forms correspond to naturally-occurring alternatively spliced forms of T cell costimulatory molecules or variants thereof which can be produced by standard recombinant DNA techniques. In one embodiment, the T cell costimulatory molecule of the invention contains a novel cytoplasmic domain. In another embodiment, the T cell costimulatory molecule of the invention contains a novel signal peptide domain or has an immunoglobulin variable region-like domain deleted. The novel structural forms of T cell costimulatory molecules can be used to identify agents which stimulate the expression of alternative forms of costimulatory molecules and to identify components of the signal transduction pathway which results in costimulation of T cells.

    摘要翻译： 描述了T细胞共刺激分子的新型结构形式。 这些结构形式包括一个新的结构域或者具有缺失或添加的结构域。 结构形式对应于可以通过标准重组DNA技术产生的天然存在的可变剪接形式的T细胞共刺激分子或其变体。 在一个实施方案中，本发明的T细胞共刺激分子含有新的细胞质结构域。 在另一个实施方案中，本发明的T细胞共刺激分子含有新的信号肽结构域或具有免疫球蛋白可变区域结构域缺失。 T细胞共刺激分子的新型结构形式可用于鉴定刺激替代形式的共刺激分子表达的试剂，并鉴定导致T细胞共刺激的信号转导通路的成分。