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    Nucleic acids encoding CD100 molecules
    11.
    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。

    Methods of inducing a T cell mediated immune response by administering antigen presenting B cells
    12.
    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。

    T cell costimulatory polypeptides containing alternative domains
    13.
    发明授权
    T cell costimulatory polypeptides containing alternative domains 失效
    含有替代结构域的T细胞共刺激多肽

    公开(公告)号：US07153934B2

    公开(公告)日：2006-12-26

    申请号：US09962969

    申请日：2001-09-24

    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： C07K14/435 ,  C07K14/705

    CPC分类号： C07K14/70532 ,  A01K2217/05

    摘要： Structural forms of T cell costimulatory polypeptides are described. These forms comprise an alternative structural domain (i.e., a structural domain having an amino acid sequence which differs from a known amino acid sequence) or have a structural domain deleted or added. The structural forms correspond to naturally-occurring alternatively spliced forms of T cell costimulatory polypeptides or variants thereof which can be produced by standard recombinant DNA techniques. In one embodiment, the T cell costimulatory polypeptide of the invention contains an alternative cytoplasmic domain. In another embodiment, the T cell costimulatory polypeptide of the invention contains an alternative signal peptide domain or has an immunoglobulin variable region-like domain deleted. The alternative structural forms of T cell costimulatory polypeptides can be used to identify agents which stimulate the expression of alternative forms of costimulatory polypeptides and to identify components of the signal transduction pathway which results in costimulation of T cells.

    摘要翻译： 描述了T细胞共刺激多肽的结构形式。 这些形式包括可选择的结构域（即，具有不同于已知氨基酸序列的氨基酸序列的结构域）或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细胞共刺激多肽或其变体。 在一个实施方案中，本发明的T细胞共刺激多肽含有替代细胞质结构域。 在另一个实施方案中，本发明的T细胞共刺激多肽含有替代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细胞共刺激多肽的替代结构形式可用于鉴定刺激替代形式的共刺激多肽的表达并鉴定导致T细胞共刺激的信号转导途径的组分的试剂。

    Polypeptides comprising a B7 extracellular domain
    14.
    发明授权
    Polypeptides comprising a B7 extracellular domain 失效
    包含B7细胞外结构域的多肽

    公开(公告)号：US06653444B1

    公开(公告)日：2003-11-25

    申请号：US08453386

    申请日：1995-05-30

    申请人： Gordon J. Freeman ,  Arnold S. Freedman ,  Lee M. Nadler

    发明人： Gordon J. Freeman ,  Arnold S. Freedman ,  Lee M. Nadler

    IPC分类号： C07K14705

    CPC分类号： C07K14/70532 ,  A01K2217/075

    摘要： Isolated nucleic acid molecules encoding a B cell activation antigen, B7, are provided. In one embodiment, the nucleic acid molecules are DNA sequences. The DNA 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 provided are host cells transformed to produce proteins or peptides encoded by the DNA molecules of the present invention and purified proteins and peptides which comprise at least a portion of the B cell activation antigen. The proteins and peptides comprise at least a portion of the mature form of the B7 activation antigen and preferably comprise a soluble form of the B7 protein.

    摘要翻译： 提供编码B细胞活化抗原B7的分离的核酸分子。 在一个实施方案中，核酸分子是DNA序列。 本发明的DNA序列可以整合到各种表达载体中，这又可以引导各种宿主，特别是真核细胞如哺乳动物和昆虫细胞培养物中相应的蛋白质或肽的合成。 还提供了转化以产生由本发明的DNA分子编码的蛋白质或肽的宿主细胞和包含至少一部分B细胞活化抗原的纯化的蛋白质和肽。 蛋白质和肽包含至少一部分成熟形式的B7活化抗原，并且优选包含可溶形式的B7蛋白。

    Tumor cells with increased immunogenicity and uses therefor
    16.
    发明授权
    Tumor cells with increased immunogenicity and uses therefor 有权
    具有增加的免疫原性的肿瘤细胞及其用途

    公开(公告)号：US06319709B1

    公开(公告)日：2001-11-20

    申请号：US09450798

    申请日：1999-11-29

    申请人： Suzanne Ostrand-Rosenberg ,  Sivasubramanian Baskar ,  Laurie H. Glimcher ,  Gordon J. Freeman ,  Lee M. Nadler

    发明人： Suzanne Ostrand-Rosenberg ,  Sivasubramanian Baskar ,  Laurie H. Glimcher ,  Gordon J. Freeman ,  Lee M. Nadler

    IPC分类号： C12N1585

    CPC分类号： A61K39/0011 ,  A61K39/00 ,  A61K48/00 ,  A61K2039/5152 ,  A61K2039/5156 ,  A61K2039/5158 ,  C07K14/70532 ,  C07K14/70539

    摘要： Tumor cells modified to express a T cell costimulatory molecule are disclosed. In one embodiment, the costimulatory molecule is a CD28/CTLA4 ligand, preferably a B lymphocyte antigen B7. The tumor cells of the invention can be modified by transfection with nucleic acid encoding a T cell costimulatory molecule, by using an agent which induces or increases expression of a T cell costimulatory molecule on the tumor cell surface or by coupling a T cell costimulatory molecule to the tumor cell surface. Tumor cells further modified to express MHC class I and/or class II molecules or in which expression of an MHC associated protein, the invariant chain, is inhibited are also disclosed. The modified tumor cells of the invention can be used in methods for treating a patient with a tumor, preventing or inhibiting metastatic spread of a tumor or preventing or inhibiting recurrence of a tumor. A method for specifically inducing a CD4+ T cell response against a tumor and a method for treating a tumor by modification of tumor cells in vivo are disclosed.

    摘要翻译： 公开了修饰以表达T细胞共刺激分子的肿瘤细胞。 在一个实施方案中，共刺激分子是CD28 / CTLA4配体，优选B淋巴细胞抗原B7。 通过使用诱导或增加T细胞共刺激分子在肿瘤细胞表面上的表达或通过将T细胞共刺激分子与T细胞共刺激分子的偶联的试剂，可以通过用编码T细胞共刺激分子的核酸转染来修饰本发明的肿瘤细胞 肿瘤细胞表面。 还公开了进一步修饰以表达MHC I类和/或II类分子或其中抑制MHC相关蛋白（不变链）的表达的肿瘤细胞。 本发明的修饰的肿瘤细胞可用于治疗患有肿瘤的患者，预防或抑制肿瘤的转移性扩散或预防或抑制肿瘤复发的方法。 公开了特异性诱导针对肿瘤的CD4 + T细胞应答的方法和通过体内修饰肿瘤细胞治疗肿瘤的方法。

    DNA encoding, B7, a new member of the IG superfamily with unique expression on activated and neoplastic B cells
    17.
    发明授权
    DNA encoding, B7, a new member of the IG superfamily with unique expression on activated and neoplastic B cells 失效
    DNA编码，B7，在活化和肿瘤B细胞上具有独特表达的IG超家族的新成员

    公开(公告)号：US6071716A

    公开(公告)日：2000-06-06

    申请号：US153262

    申请日：1993-11-15

    申请人： Gordon J. Freeman ,  Arnold S. Freedman ,  Lee M. Nadler

    发明人： Gordon J. Freeman ,  Arnold S. Freedman ,  Lee M. Nadler

    IPC分类号： C07K14/705 ,  C12N15/12 ,  C12N15/00

    CPC分类号： C07K14/70532 ,  A01K2217/075

    摘要： Isolated nucleic acid molecules encoding a B cell activation antigen, B7, are provided. In one embodiment, the nucleic acid molecules are DNA sequences. The DNA 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 provided are host cells transformed to produce proteins or peptides encoded by the DNA molecules of the present invention and purified proteins and peptides which comprise at least a portion of the B cell activation antigen. The proteins and peptides comprise at least a portion of the mature form of the B7 activation antigen and preferably comprise a soluble form of the B7 protein.

    摘要翻译： 提供编码B细胞活化抗原B7的分离的核酸分子。 在一个实施方案中，核酸分子是DNA序列。 本发明的DNA序列可以整合到各种表达载体中，这又可以引导各种宿主，特别是真核细胞如哺乳动物和昆虫细胞培养物中相应的蛋白质或肽的合成。 还提供了转化以产生由本发明的DNA分子编码的蛋白质或肽的宿主细胞和包含至少一部分B细胞活化抗原的纯化的蛋白质和肽。 蛋白质和肽包含至少一部分成熟形式的B7活化抗原，并且优选包含可溶形式的B7蛋白。

    Nucleic acid molecules encoding B7-1
    19.
    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。

    Method of promoting b-cell proliferation and activation with CD40 ligand and cyclosporin
    20.
    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。