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    Chimeric Fc-gamma Receptor and Method for Determination of ADCC Activity by Using the Receptor
    4.
    发明申请
    Chimeric Fc-gamma Receptor and Method for Determination of ADCC Activity by Using the Receptor 有权
    嵌合Fc-γ受体和使用受体测定ADCC活性的方法

    公开(公告)号：US20100035280A1

    公开(公告)日：2010-02-11

    申请号：US12525031

    申请日：2008-01-30

    申请人： Shigeto Kawai

    发明人： Shigeto Kawai

    IPC分类号： G01N33/567 ,  C07K14/705 ,  C07H21/04 ,  C12N15/63 ,  C12N5/10

    CPC分类号： G01N33/566 ,  C07K14/70535 ,  C07K16/18 ,  C07K2317/24 ,  C07K2317/41 ,  C07K2317/52 ,  C07K2317/732 ,  C07K2319/00 ,  G01N33/5014 ,  G01N2500/04 ,  G01N2500/10

    摘要： An objective of the present invention is to provide chimeric receptors containing a mouse Fcγ receptor extracellular domain and a human Fcγ receptor transmembrane domain, or chimeric receptors containing a mouse Fcγ receptor extracellular domain and a human γ chain transmembrane domain. Another objective of the present invention is to provide methods for measuring the ADCC activity of mouse antibodies and methods of screening for mouse antibodies having ADCC activity, using the chimeric receptors.To accomplish the above-mentioned objectives, the present inventors produced chimeric molecules by fusing the extracellular domain of mouse FcγR3 or mouse FcγR4 with the transmembrane domain/intracellular domain of human γ chain or human FcγR3, and expressed the chimeric molecules in human NK92 cells. It was revealed that the ADCC activity can be induced by the chimeric receptors produced by any combination of the domains, and that the ADCC activity of mouse antibodies can be measured using the chimeric receptors of the present invention.

    摘要翻译： 本发明的目的是提供含有小鼠Fcγ受体细胞外结构域和人Fcγ受体跨膜结构域的嵌合受体或含有小鼠Fcγ受体细胞外结构域和人γ链跨膜结构域的嵌合受体。 本发明的另一个目的是提供使用嵌合受体测量小鼠抗体的ADCC活性的方法和筛选具有ADCC活性的小鼠抗体的方法。 为了实现上述目的，本发明人通过将小鼠FcgammaR3或小鼠FcγR4的细胞外结构域与人γ链或人FcγR3的跨膜结构域/细胞内结构域融合而产生嵌合分子，并在人NK92细胞中表达嵌合分子。 显示AD​​CC活性可以由通过结构域的任何组合产生的嵌合受体诱导，并且可以使用本发明的嵌合受体来测量小鼠抗体的ADCC活性。

    Cell death-inducing agent
    6.
    发明申请
    Cell death-inducing agent 失效
    细胞死亡诱导剂

    公开(公告)号：US20060275301A1

    公开(公告)日：2006-12-07

    申请号：US10530696

    申请日：2003-10-10

    申请人： Shuji Ozaki ,  Masahiro Abe ,  Masayuki Tsuchiya ,  Naoki Kimura ,  Shigeto Kawai

    发明人： Shuji Ozaki ,  Masahiro Abe ,  Masayuki Tsuchiya ,  Naoki Kimura ,  Shigeto Kawai

    IPC分类号： A61K39/395 ,  C07K16/30

    CPC分类号： C07K16/2833 ,  A61K2039/505 ,  C07K14/70539 ,  C07K2317/34 ,  C07K2317/565 ,  C07K2317/626 ,  C07K2317/73

    摘要： To identify antigens of the 2D7 antibody, the present inventors cloned the 2D7 antigen. The results suggested that the 2D7 antigen is an HLA class I molecule. Based on this finding, the present inventors examined whether the 2D7 antibody has cell death-inducing activity. Nuclei fragmentation was observed when the 2D7 antibody was cross-linked with another antibody, indicating that cell-death was induced. Further, diabodies of the 2D7 antibody were found to have very strong cell death-inducing activities, even without the addition of another antibody. These results indicate that minibodies of an HLA-recognizing antibody can be used as cell death-inducing agents.

    摘要翻译： 为了鉴定2D7抗体的抗原，本发明人克隆了2D7抗原。 结果表明，2D7抗原是HLA I类分子。 基于该发现，本发明人检查了2D7抗体是否具有细胞死亡诱导活性。 当2D7抗体与另一种抗体交联时，观察到细胞核碎裂，表明诱导细胞死亡。 此外，发现2D7抗体的双抗体具有非常强的细胞死亡诱导活性，即使没有添加另一种抗体。 这些结果表明HLA识别抗体的小体抗体可以用作细胞死亡诱导剂。