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    ANTI-WT1/HLA BI-SPECIFIC ANTIBODY
    4.
    发明申请
    ANTI-WT1/HLA BI-SPECIFIC ANTIBODY 审中-公开
    ANTI-WT1 / HLA BI特异性抗体

    公开(公告)号：US20160280796A1

    公开(公告)日：2016-09-29

    申请号：US15034782

    申请日：2014-11-07

    申请人： MEMORIAL SLOAN-KETTERING CANCER CENTER ,  EUREKA THERAPEUTICS, INC.

    发明人： David Scheinberg ,  Jingyi Xiang ,  Tao Dao ,  Su Yan ,  Cheng Liu

    IPC分类号： C07K16/32 ,  C07K16/28

    CPC分类号： C07K16/32 ,  A61K2039/505 ,  C07K16/2809 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2317/622 ,  C07K2317/73

    摘要： Disclosed herein is a bi-specific form of a T cell receptor mimic (TCRm) mAb with reactivity to human immune effector cell antigen and a WT1 peptide/HLA-A epitope. This antibody selectively bound to leukemias and solid tumor cells expressing WT1 and HLA-A as well as activated resting human T cells to release interferon-(IFN-γ) and to kill the target cancer cells in vitro. Importantly, the antibody mediated autologous T cell proliferation and directed potent cytotoxicity against fresh ovarian cancer cells. Therapeutic activity in vivo of the antibody was demonstrated in NOD SCID SCID Yc* (NSG) mice with three different human cancers expressing WT1/HLA-A2 including disseminated Ph+ acute lymphocytic leukemia (ALL), disseminated acute myeloid leukemia, and peritoneal mesothelioma. In both of the leukemia xenograft models, mice that received the antibody and T cells also showed longer survival and delayed limb paralysis. Also provided are methods for stimulating a primary T cell response comprising stimulating cytotoxic T cells against a first tumor antigen and a secondary T cell response comprising stimulating effector T cells and/or memory T cells against a first tumor antigen and/or against a second tumor antigen using the bi-specific antibodies described herein.

    摘要翻译： 本文公开了与人免疫效应细胞抗原和WT1肽/ HLA-A表位具有反应性的T细胞受体模拟物（TCRm）mAb的双特异性形式。 该抗体选择性结合表达WT1和HLA-A的白血病和实体肿瘤细胞以及活化的休息的人T细胞以释放干扰素（IFN-γ）并在体外杀死靶癌细胞。 重要的是，抗体介导的自体T细胞增殖和对新鲜卵巢癌细胞的有力的细胞毒性。 在具有表达WT1 / HLA-A2的三种不同人类癌症的NOD SCID SCID Yc *（NSG）小鼠中证实了抗体的治疗活性，包括播散性Ph +急性淋巴细胞性白血病（ALL），弥散性急性骨髓性白血病和腹膜间皮瘤。 在两种白血病异种移植模型中，接受抗体和T细胞的小鼠也显示较长的存活期和延迟的肢体麻痹。 还提供了用于刺激原代T细胞应答的方法，包括刺激针对第一肿瘤抗原的细胞毒性T细胞和辅助T细胞应答，包括针对第一肿瘤抗原和/或针对第二肿瘤刺激效应T细胞和/或记忆T细胞 使用本文所述的双特异性抗体。

    Anti-WT1/HLA bi-specific antibody
    7.
    发明授权
    Anti-WT1/HLA bi-specific antibody 有权

    公开(公告)号：US10239952B2

    公开(公告)日：2019-03-26

    申请号：US15034782

    申请日：2014-11-07

    申请人： MEMORIAL SLOAN-KETTERING CANCER CENTER ,  EUREKA THERAPEUTICS, INC.

    发明人： David Scheinberg ,  Jingyi Xiang ,  Tao Dao ,  Su Yan ,  Cheng Liu

    IPC分类号： A61K39/00 ,  C07K16/32 ,  C07K16/28

    摘要： Disclosed herein is a bi-specific form of a T cell receptor mimic (TCRm) mAb with reactivity to human immune effector cell antigen and a WT1 peptide/HLA-A epitope. This antibody selectively bound to leukemias and solid tumor cells expressing WT1 and HLA-A as well as activated resting human T cells to release interferon-(IFN-γ) and to kill the target cancer cells in vitro. Importantly, the antibody mediated autologous T cell proliferation and directed potent cytotoxicity against fresh ovarian cancer cells. Therapeutic activity in vivo of the antibody was demonstrated in NOD SCID SCID Yc*(NSG) mice with three different human cancers expressing WT1/HLA-A2 including disseminated Ph+ acute lymphocytic leukemia (ALL), disseminated acute myeloid leukemia, and peritoneal mesothelioma. In both of the leukemia xenograft models, mice that received the antibody and T cells also showed longer survival and delayed limb paralysis. Also provided are methods for stimulating a primary T cell response comprising stimulating cytotoxic T cells against a first tumor antigen and a secondary T cell response comprising stimulating effector T cells and/or memory T cells against a first tumor antigen and/or against a second tumor antigen using the bi-specific antibodies described herein.