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

    公开(公告)号：EP3066130A1

    公开(公告)日：2016-09-14

    申请号：EP14803300.4

    申请日：2014-11-07

    申请人： Memorial Sloan Kettering Cancer Center ,  Eureka Therapeutics, Inc.

    发明人： SCHEINBERG, David ,  XIANG, Jingyi ,  DAO, Tao ,  YAN, Su ,  LIU, Cheng

    IPC分类号： C07K16/32 ,  C07K16/28 ,  C07K16/46 ,  A61K39/395 ,  A61P35/00 ,  A61P35/02

    CPC分类号： C07K16/32 ,  A61K2039/505 ,  C07K16/2809 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/92 ,  C07K2317/94 ,  C07K2319/00

    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.

    T CELL RECEPTOR-LIKE ANTIBODIES SPECIFIC FOR A WT1 PEPTIDE PRESENTED BY HLA-A2
    9.
    发明公开
    T CELL RECEPTOR-LIKE ANTIBODIES SPECIFIC FOR A WT1 PEPTIDE PRESENTED BY HLA-A2 有权
    T细胞受体抗体特异性相似由HLA-A2呈现WT1肽

    公开(公告)号：EP2694553A2

    公开(公告)日：2014-02-12

    申请号：EP12726511.4

    申请日：2012-04-02

    申请人： Memorial Sloan-Kettering Cancer Center

    发明人： SCHEINBERG, David A. ,  DAO, Tao ,  LIU, Cheng ,  YAN, Su

    IPC分类号： C07K16/28

    CPC分类号： C07K16/32 ,  A61K47/6849 ,  A61K47/6851 ,  A61K2039/505 ,  C07K16/18 ,  C07K16/2833 ,  C07K2317/21 ,  C07K2317/34 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/622 ,  C07K2317/732 ,  G01N33/5748

    摘要： The present invention provides antigen binding proteins that specifically bind to Wilms' tumor protein (WT1), including humanized, chimeric and fully human antibodies against WT1, antibody fragments, chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen binding proteins and antibodies bind to HLA-A0201-restricted WT1 peptide. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of WT1 associated cancers, including for example, breast cancer, ovarian cancer, prostate cancer, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). In more particular embodiments, the anti-WT1/A antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels.

    摘要翻译： 本发明提供了抗原结合蛋白特异性结合做以维尔姆斯肿瘤蛋白（WT1），包括针对WT1人源化的，嵌合的和完全人抗体，抗体片段，嵌合抗原受体（CARS）的融合蛋白，和缀合物。 抗原结合蛋白和抗体结合到HLA-A0201限制性WT1肽。 搜索抗体，片段，融合蛋白和缀合物是用于WT1相关的癌症的治疗中是有用的，包括，例如，乳腺癌，卵巢癌，前列腺癌，慢性髓细胞性白血病，多发性骨髓瘤，急性淋巴细胞白血病（ALL），急性髓细胞性/ 髓细胞性白血病（AML）和骨髓增生异常综合征（MDS）。 在更具体的实施方案中，抗WT1 / A抗体可以包含设计用于提高蛋白质稳定性的一个或多个氨基酸取代的框架区，抗体结合和/或表达水平。