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    Tumor cells modified to express B7-2 with increased immunogenicity and uses therefor
    21.
    发明授权
    Tumor cells modified to express B7-2 with increased immunogenicity and uses therefor 失效
    肿瘤细胞修饰以表达B7-2，增加免疫原性，并用于此

    公开(公告)号：US5861310A

    公开(公告)日：1999-01-19

    申请号：US456104

    申请日：1995-05-30

    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： A01K67/027 ,  A61K38/00 ,  C07K14/705 ,  C07K16/28 ,  C12N15/85 ,  C12N5/00 ,  C12N5/08 ,  C12N5/10

    CPC分类号： C07K16/2827 ,  A01K67/0271 ,  C07K14/70532 ,  C12N15/8509 ,  A01K2217/05 ,  A01K2267/0331 ,  A01K2267/0381 ,  A61K38/00 ,  C07K2319/30

    摘要： Tumor cells modified to express one or more T cell costimulatory molecules are disclosed. Preferred costimulatory molecules are B7-2 and B7-3. The tumor cells of the invention can be modified by transfection with nucleic acid encoding B7-2 and/or B7-3, by using an agent which induces or increases expression of B7-2 and/or B7-3 on the tumor cell or by coupling B7-2 and/or B7-3 to the tumor cell. Tumor cells modified to express B7-2 and/or B7-3 can be further modified to express B7. 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.sup.+ 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： 公开了修饰以表达一种或多种T细胞共刺激分子的肿瘤细胞。 优选的共刺激分子是B7-2和B7-3。 本发明的肿瘤细胞可以通过用编码B7-2和/或B7-3的核酸转染，通过使用诱导或增加肿瘤细胞上B7-2和/或B7-3表达的试剂或通过 将B7-2和/或B7-3偶联到肿瘤细胞。 修饰以表达B7-2和/或B7-3的肿瘤细胞可进一步修饰以表达B7。 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。

    Nucleic acids encoding B7-2 fusion proteins
    22.
    发明授权
    Nucleic acids encoding B7-2 fusion proteins 失效
    编码B7-2融合蛋白的核酸

    公开(公告)号：US07459544B2

    公开(公告)日：2008-12-02

    申请号：US10429079

    申请日：2003-05-02

    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： C07H21/04

    CPC分类号： C07K16/2827 ,  A01K67/0276 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2217/30 ,  A01K2227/105 ,  A01K2267/01 ,  A01K2267/03 ,  A01K2267/0325 ,  A01K2267/0331 ,  A01K2267/0381 ,  A61K38/00 ,  C07K14/70503 ,  C07K14/70532 ,  C07K2317/73 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/30 ,  C12N15/8509

    摘要： Nucleic acids encoding novel CTLA4/CD28 ligands which costimulate T cell activation are disclosed. In one embodiment, the nucleic acid has a sequence which encodes a B lymphocyte 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 or FIG. 14, SEQ ID NO:23. The nucleic acid sequences of the invention can be integrated into various expression vectors, which in turn 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. Proteins and peptides described herein can be administered to subjects to enhance or suppress T cell-mediated immune responses.

    摘要翻译： 公开了编码协同T细胞活化的新型CTLA4 / CD28配体的核酸。 在一个实施方案中，核酸具有编码B淋巴细胞抗原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或图3。 14，SEQ ID NO：23。 本发明的核酸序列可以整合到各种表达载体中，这又指导了多种宿主，特别是真核细胞如哺乳动物和昆虫细胞培养物中的相应蛋白质或肽的合成。 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。 本文所述的蛋白质和肽可以施用于受试者以增强或抑制T细胞介导的免疫应答。

    T cell costimulatory polypeptides containing alternative domains
    23.
    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。

    Methods for inhibiting the interaction of B7-2 with its natural ligand
    24.
    发明授权
    Methods for inhibiting the interaction of B7-2 with its natural ligand 失效
    抑制B7-2与天然配体相互作用的方法

    公开(公告)号：US06824779B1

    公开(公告)日：2004-11-30

    申请号：US09425516

    申请日：1999-10-22

    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： A61K39395

    CPC分类号： A01K67/0276 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2217/30 ,  A01K2227/105 ,  A01K2267/0325 ,  A01K2267/0331 ,  A61K38/00 ,  C07K14/70503 ,  C07K14/70532 ,  C07K16/2827 ,  C07K2317/73 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/30 ,  C12N15/8509

    摘要： The present invention relates to, inter alia, methods for inhibiting the interaction of the B-lymphocyte antigen, B7-2, with its natural ligand on the surface of an immune cell are disclosed. The methods comprise contacting the immune cell with an agent which inhibits B7-2 binding with its natural ligand, to thereby inhibit the interaction. Examples of such agents are provided, and include a soluble form of B7-2, an antibody that recognized B7-2. The method may also include contacting the immune cell with an agent that blocks the interaction of B7-1 with its natural ligand. Further, the method may include contacting the immune cell with an immunomodulating agent, for example, an antibody reactive with CD28, an antibody reactive with CTLA4, an antibody reactive with a cytokine, a CTLA4Ig fusion protein, a CD28Ig fusion protein, and an immunosuppressive drug. Both in vivo and in vitro applications of the method are disclosed.

    摘要翻译： 本发明尤其涉及用于抑制B淋巴细胞抗原B7-2与其天然配体在免疫细胞表面上的相互作用的方法。 所述方法包括使免疫细胞与抑制B7-2与其天然配体结合的试剂接触，从而抑制相互作用。 提供这些试剂的实例，并且包括可溶形式的B7-2，其是识别B7-2的抗体。 该方法还可以包括使免疫细胞与阻断B7-1与其天然配体的相互作用的试剂接触。 此外，该方法可以包括使免疫细胞与免疫调节剂接触，例如与CD28反应的抗体，与CTLA4反应的抗体，与细胞因子反应的抗体，CTLA4Ig融合蛋白，CD28Ig融合蛋白和免疫抑制 药物。 公开了该方法的体内和体外应用。

    Polypeptides comprising a B7 extracellular domain
    25.
    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
    27.
    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
    28.
    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。