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    CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor
    1.
    发明授权
    CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor 失效
    具有修饰的效应子功能的CTLA4-免疫球蛋白融合蛋白及其用途

    公开(公告)号：US06750334B1

    公开(公告)日：2004-06-15

    申请号：US08595590

    申请日：1996-02-02

    申请人： Gary S. Gray ,  Jerry Carson ,  Kashi Javaherian ,  Cindy L. Jellis ,  Paul D. Rennert ,  Sandra Silver

    发明人： Gary S. Gray ,  Jerry Carson ,  Kashi Javaherian ,  Cindy L. Jellis ,  Paul D. Rennert ,  Sandra Silver

    IPC分类号： C07H2104

    CPC分类号： C07K14/70503 ,  A61K38/00 ,  A61K2039/5154 ,  C07K2319/00

    摘要： CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g., CD28 and/or CTLA4) on the surface of T cells to thereby suppress an immune response in the subject, for example to inhibit transplantation rejection, graft versus host disease or autoimmune responses.

    摘要翻译： 描述了具有修饰的免疫球蛋白恒定区介导的效应子功能的CTLA4-免疫球蛋白融合蛋白，以及编码融合蛋白的核酸。 CTLA4免疫球蛋白融合蛋白包含两个组分：具有CTLA4活性的第一肽和包含免疫球蛋白恒定区的第二个肽，其被修饰以相对于CTLA4-IgG1融合蛋白减少至少一个恒定区介导的生物效应子功能。 本发明的核酸可以整合到各种表达载体中，这又可以指导各种宿主，特别是真核细胞中相应的蛋白质的合成。 本文所述的CTLA4-免疫球蛋白融合蛋白可以施用于受试者以抑制抗原呈递细胞上的CTLA4配体（例如B7-1和/或B7-2）与CTLA4配体的受体（例如， CD28和/或CTLA4），从而抑制受试者的免疫应答，例如抑制移植排斥反应，移植物抗宿主病或自身免疫应答。

    CTLA4-C&ggr;4 fusion proteins
    2.
    发明授权
    CTLA4-C&ggr;4 fusion proteins 失效
    CTLA4-Cgamma4融合蛋白

    公开(公告)号：US06444792B1

    公开(公告)日：2002-09-03

    申请号：US09227595

    申请日：1999-01-08

    申请人： Gary S. Gray ,  Jerry Carson ,  Kashi Javaherian ,  Paul D. Rennert ,  Sandra Silver

    发明人： Gary S. Gray ,  Jerry Carson ,  Kashi Javaherian ,  Paul D. Rennert ,  Sandra Silver

    IPC分类号： A61K39395

    CPC分类号： C07K14/70503 ,  A61K38/00 ,  A61K2039/5154 ,  C07K2319/00

    摘要： CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g., CD28 and/or CTLA4) on the surface of T cells to thereby suppress an immune response in the subject, for example to inhibit transplantation rejection, graft versus host disease or autoimmune responses.

    摘要翻译： 描述了具有修饰的免疫球蛋白恒定区介导的效应子功能的CTLA4-免疫球蛋白融合蛋白，以及编码融合蛋白的核酸。 CTLA4免疫球蛋白融合蛋白包含两个组分：具有CTLA4活性的第一肽和包含免疫球蛋白恒定区的第二个肽，其被修饰以相对于CTLA4-IgG1融合蛋白减少至少一个恒定区介导的生物效应子功能。 本发明的核酸可以整合到各种表达载体中，这又可以指导各种宿主，特别是真核细胞中相应的蛋白质的合成。 本文所述的CTLA4-免疫球蛋白融合蛋白可以施用于受试者以抑制抗原呈递细胞上的CTLA4配体（例如B7-1和/或B7-2）与CTLA4配体的受体（例如， CD28和/或CTLA4），从而抑制受试者的免疫应答，例如抑制移植排斥反应，移植物抗宿主病或自身免疫应答。

    Methods for selectively enriching TH1 and TH2 cells
    9.
    发明授权
    Methods for selectively enriching TH1 and TH2 cells 失效
    选择性富集TH1和TH2细胞的方法

    公开(公告)号：US07479269B2

    公开(公告)日：2009-01-20

    申请号：US11326148

    申请日：2006-01-05

    申请人： Carl H. June ,  Craig B. Thompson ,  Gary J. Nabel ,  Gary S. Gray ,  Paul D. Rennert

    发明人： Carl H. June ,  Craig B. Thompson ,  Gary J. Nabel ,  Gary S. Gray ,  Paul D. Rennert

    IPC分类号： A61K35/14 ,  A61K35/26 ,  A61K35/28

    CPC分类号： C07K16/2809 ,  A61K35/17 ,  A61K2039/507 ,  C07K16/2806 ,  C07K16/2818 ,  C07K2317/34 ,  C07K2317/55 ,  C07K2317/74 ,  C07K2319/30 ,  C12N2740/16011

    摘要： Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.

    摘要翻译： 描述了通过激活T细胞群并用结合附属分子的配体刺激T细胞表面上的辅助分子来诱导T细胞群体增殖的方法。 T细胞增殖发生在没有外源生长因子或附属细胞的情况下。 通过刺激T细胞受体（TCR）/ CD3复合物或CD2表面蛋白来完成T细胞活化。 为了诱导活化的群体T细胞的增殖，T细胞表面上的辅助分子如CD28被与配合分子结合的配体刺激。 通过本发明的方法扩增的T细胞群体可以被遗传转导并用于免疫治疗，或可用于诊断方法。

    Methods for selectively stimulating proliferation of T cells
    10.
    发明授权
    Methods for selectively stimulating proliferation of T cells 有权
    选择性刺激T细胞增殖的方法

    公开(公告)号：US07175843B2

    公开(公告)日：2007-02-13

    申请号：US11366331

    申请日：2006-03-02

    申请人： Carl H. June ,  Craig B. Thompson ,  Gary J. Nabel ,  Gary S. Gray ,  Paul D. Rennert

    发明人： Carl H. June ,  Craig B. Thompson ,  Gary J. Nabel ,  Gary S. Gray ,  Paul D. Rennert

    IPC分类号： A61K35/14 ,  A61K35/26 ,  A61K35/28

    CPC分类号： C07K14/705 ,  A61K2039/5158 ,  C07K16/2806 ,  C07K16/2809 ,  C07K16/2818 ,  C07K16/2896 ,  C07K2317/34 ,  C12N5/0636 ,  C12N2501/51 ,  C12N2501/515 ,  C12N2501/599

    摘要： Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.

    摘要翻译： 描述了通过激活T细胞群并用结合附属分子的配体刺激T细胞表面上的辅助分子来诱导T细胞群体增殖的方法。 T细胞增殖发生在没有外源生长因子或附属细胞的情况下。 通过刺激T细胞受体（TCR）/ CD3复合物或CD2表面蛋白来完成T细胞活化。 为了诱导活化的群体T细胞的增殖，T细胞表面上的辅助分子如CD28被与配合分子结合的配体刺激。 通过本发明的方法扩增的T细胞群体可以被遗传转导并用于免疫治疗，或可用于诊断方法。