利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

23 条记录 (耗时 0.021 秒)

    Methods of inhibiting T cell proliferation or IL-2 accumulation with CTLA-4 specific antibodies
    8.
    发明授权
    Methods of inhibiting T cell proliferation or IL-2 accumulation with CTLA-4 specific antibodies 失效
    用CTLA-4特异性抗体抑制T细胞增殖或IL-2积累的方法

    公开(公告)号：US07592007B2

    公开(公告)日：2009-09-22

    申请号：US10732847

    申请日：2003-12-09

    申请人： John G. Gribben ,  Gordon J. Freeman ,  Lee M. Nadler ,  Paul Rennert ,  Cindy L. Jellis ,  Edward Greenfield ,  Gary S. Gray

    发明人： John G. Gribben ,  Gordon J. Freeman ,  Lee M. Nadler ,  Paul Rennert ,  Cindy L. Jellis ,  Edward Greenfield ,  Gary S. Gray

    IPC分类号： A61K39/395 ,  C07K16/28

    CPC分类号： C07K14/70521 ,  A61K38/00 ,  C07K14/70532 ,  C07K16/2818 ,  C07K2317/34

    摘要： Isolated ligands which bind a molecule expressed on the surface of T cells and induce antigen specific apoptosis in activated T cells are disclosed. Preferably, the T cell surface molecule is CTLA4 and the ligand is a monoclonal anti-CTLA4 antibody that binds to an epitope of CTLA4 distinct from the binding sites of B7-1 and B7-2. Upon binding of the antibody to CTLA4 on an activated T cell, in the presence of an antigenic signal, antigen specific apoptosis is induced. The invention also describes a novel natural CTLA4 ligand, distinct from B7-1 and B7-2, which mediates induction of apoptosis. Pharmaceutical compositions of anti-CTLA4 antibodies or other isolated CTLA4 ligands which can be administered to subjects to induce T cell apoptosis, thereby clonally deleting antigen specific T cells, such as alloreactive T cells in transplantation situations or autoreactive T cells in autoimmune disorders, are also disclosed. Methods for inducing T cell apoptosis in vitro with an anti-CTLA4 antibody or other ligand of the invention together with an antigen specific signal are also disclosed, e.g., for use in purging alloreactive T cells from donor bone marrow prior to bone marrow transplantation to inhibit graft versus host disease.

    摘要翻译： 公开了结合在T细胞表面上表达并在活化的T细胞中诱导抗原特异性凋亡的分子的分离的配体。 优选地，T细胞表面分子是CTLA4，并且配体是结合与B7-1和B7-2的结合位点不同的CTLA4的表位的单克隆抗CTLA4抗体。 当抗体与CTLA4在活化的T细胞上结合时，在抗原信号存在下，诱导抗原特异性凋亡。 本发明还描述了一种与介导细胞凋亡诱导的B7-1和B7-2不同的新型天然CTLA4配体。 抗CTLA4抗体或其他分离的CTLA4配体的药物组合物也可以被给予受试者诱导T细胞凋亡，从而克隆地删除抗原特异性T细胞，例如移植情况下的同种异体反应性T细胞或自身免疫性疾病中的自身反应性T细胞， 披露 还公开了用本发明的抗CTLA4抗体或其他配体与抗原特异性信号一起体外诱导T细胞凋亡的方法，例如用于在骨髓移植之前从供体骨髓中清除同种异体反应性T细胞以抑制 移植物抗宿主病。