发明名称 |
ANTI-WT1/HLA BI-SPECIFIC ANTIBODY |
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. |
申请公布号 |
EP3066130(A1) |
申请公布日期 |
2016.09.14 |
申请号 |
EP20140803300 |
申请日期 |
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 |
分类号 |
C07K16/32;A61K39/395;A61P35/00;A61P35/02;C07K16/28;C07K16/46 |
主分类号 |
C07K16/32 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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