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    METHODS OF INDUCING A T CELL MEDIATED IMMUNE RESPONSE BY ADMINISTERING ANTIGEN PRESENTING B CELLS
    2.
    发明申请
    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：US20070031811A1

    公开(公告)日：2007-02-08

    申请号：US10186416

    申请日：2002-07-01

    申请人： Joachim Schultze ,  Gordon Freeman ,  John Gribben ,  Lee Nadler

    发明人： Joachim Schultze ,  Gordon Freeman ,  John Gribben ,  Lee Nadler

    IPC分类号： A01N1/02 ,  C12N5/08

    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。

    Novel forms of T cell costimulatory molecules and uses therefor
    4.
    发明申请
    Novel forms of T cell costimulatory molecules and uses therefor 失效
    新型形式的T细胞共刺激分子及其用途

    公开(公告)号：US20070106070A1

    公开(公告)日：2007-05-10

    申请号：US11589275

    申请日：2006-10-26

    申请人： Arlene Sharpe ,  Francescopaolo Borriello ,  Gordon Freeman ,  Lee Nadler

    发明人： Arlene Sharpe ,  Francescopaolo Borriello ,  Gordon Freeman ,  Lee Nadler

    IPC分类号： C07H21/04

    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。

    Tumor cells modified to express B7-2 with increased immunogenicity and uses therefor
    5.
    发明申请
    Tumor cells modified to express B7-2 with increased immunogenicity and uses therefor 审中-公开
    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：US20050129670A1

    公开(公告)日：2005-06-16

    申请号：US10767561

    申请日：2004-01-28

    申请人： Gordon Freeman ,  Lee Nadler ,  Gary Gray

    发明人： Gordon Freeman ,  Lee Nadler ,  Gary Gray

    IPC分类号： A01K67/027 ,  A61K38/00 ,  C07K14/705 ,  C07K16/28 ,  C12N15/85 ,  A61K48/00

    CPC分类号： C12N15/8509 ,  A01K67/0271 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/03 ,  A61K38/00 ,  C07K14/70532 ,  C07K16/2827 ,  C07K2319/00 ,  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+ 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。

    pH-triggered microparticles
    6.
    发明申请
    pH-triggered microparticles 审中-公开
    pH触发微粒

    公开(公告)号：US20050123596A1

    公开(公告)日：2005-06-09

    申请号：US10948981

    申请日：2004-09-23

    申请人： Daniel Kohane ,  Daniel Anderson ,  Robert Langer ,  William Haining ,  Lee Nadler

    发明人： Daniel Kohane ,  Daniel Anderson ,  Robert Langer ,  William Haining ,  Lee Nadler

    IPC分类号： A61K9/00 ,  A61K9/127 ,  A61K9/14 ,  A61K9/16 ,  A61K9/50 ,  A61K9/51 ,  A61K39/00 ,  A61K48/00 ,  A61L27/18 ,  C12N5/08 ,  C12N15/87 ,  C12N15/88

    CPC分类号： A61K9/1647 ,  A61K9/1617 ,  A61K9/1623 ,  A61K9/1658 ,  A61K9/5031 ,  A61K9/5153 ,  A61K9/5192

    摘要： Microparticles that are designed to release their payload when exposed to acidic conditions are provided as a vehicle for drug delivery. Any therapeutic, diagnostic, or prophylatic agent may be encapsulated in a lipid-protein-sugar or polymeric matrix including a pH triggering agent to form pH triggerable microparticles. Preferably the diameter of the pH triggered microparticles ranges from 50 nm to 10 micrometers. The matrix of the particles may be prepared using any known lipid (e.g., DPPC), protein (e.g., albumin), or sugar (e.g., lactose). The matrix of the particles may also be prepared using any synthetic polymers such as polyesters. Methods of preparing and administering the particles are provided. Methods of immunization, transfection, and gene therapy are also provided by administering pH triggerable microparticles.

    摘要翻译： 被设计为在暴露于酸性条件下释放其有效载荷的微粒被提供作为用于药物递送的载体。 任何治疗，诊断或预防剂可以包封在包含pH引发剂的脂质蛋白质糖或聚合物基质中以形成pH可触发的微粒。 优选地，pH触发的微粒的直径范围为50nm至10微米。 可以使用任何已知的脂质（例如DPPC），蛋白质（例如白蛋白）或糖（例如乳糖）来制备颗粒的基质。 颗粒的基质也可以使用任何合成聚合物如聚酯来制备。 提供了制备和施用颗粒的方法。 免疫，转染和基因治疗的方法也通过施用pH可触发的微粒来提供。

    Tumor cells with increased immunogenicity and uses therfor
    8.
    发明申请
    Tumor cells with increased immunogenicity and uses therfor 有权
    肿瘤细胞具有增加的免疫原性，并使用其它药物

    公开(公告)号：US20060099195A1

    公开(公告)日：2006-05-11

    申请号：US11313556

    申请日：2005-12-20

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

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

    IPC分类号： A61K48/00

    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。