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公开(公告)号：EP3066131A1
公开(公告)日：2016-09-14
申请号：EP14810051.4
申请日：2014-11-07
发明人： SCHEINBERG, David , VEOMETT, Nicholas , LIU, Hong , XIANG, Jingyi , LIU, Cheng , DAO, Tao , HUET, Heather, Adkins
IPC分类号： C07K16/32 , A61K39/395 , A61P35/00 , A61P35/02 , A01K67/027
CPC分类号： C07K16/32 , A01K2227/105 , A01K2267/0387 , A61K2039/505 , C07K2317/21 , C07K2317/41 , C07K2317/72 , C07K2317/732 , C07K2317/92 , C07K2317/94
摘要： The present disclosure relates to an anti-WT-1/HLA/A2 antibody with enhanced antibody dependent cell-mediated cytotoxicity (ADCC) function due to altered Fc glycosylation. The antibody, which has reduced fucose and/or galactose, was compared to its normally glycosylated counterpart in binding assays,
in vitro ADCC assays, and mesothelioma and leukemia therapeutic models and pharmacokinetic studies in mice. The antibody with normal glycosylation mediated ADCC against hematopoietic and solid tumor cells at concentrations below 1 μg/ml, but the reduced fucosylated antibody was about 5-10 fold more potent
in vitro against multiple cancer cell lines, was more potent
in vivo against JMN mesothelioma, and effective against SET2 AML and fresh ALL xenografts. ESKM had a shortened half-life (4.9
vs 6.5 days), but an identical biodistribution pattern in C57BL6/J mice. At therapeutic doses of ESKM, there was no difference in half-life or biodistribution in HLA-A2.1 + transgenic mice compared to the parent strain. Importantly, therapeutic doses of ESKM in these mice caused no depletion of total WBCs or hematopoetic stem cells, or pathologic tissue damage.-
公开(公告)号：EP3066130B1
公开(公告)日：2019-05-15
申请号：EP14803300.4
申请日：2014-11-07
发明人： SCHEINBERG, David , XIANG, Jingyi , DAO, Tao , YAN, Su , LIU, Cheng
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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
发明人： SCHEINBERG, David , XIANG, Jingyi , DAO, Tao , YAN, Su , LIU, Cheng
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.
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公开(公告)号：EP3377516A1
公开(公告)日：2018-09-26
申请号：EP16867262.4
申请日：2016-11-18
发明人： SCHEINBERG, David
CPC分类号： A61K39/001153 , A61K39/00 , A61K39/0011 , A61K39/3955 , A61K2039/505 , A61K2039/5154 , A61K2039/5158 , A61K2039/54 , A61K2039/55505 , A61K2039/55522 , A61K2039/892 , A61P35/00 , C07K14/47 , C07K14/4748 , C07K14/82
摘要： This invention provides methods of treating, reducing the incidence of, and inducing immune responses to a WT1-expressing cancer, by administering a combination of at least one WT1 peptide, or cytotoxic T cells (CTLs) against a WT1-expressing cancer, and at least one checkpoint inhibitor. The at least one WT1 peptide can be administered to the subject by administering one or more agents to the subject resulting in delivery of one or more WT1 peptides and induction of an immune response against the WT1-expressing cancer. Examples of these WT1 delivery agents include: (i) an isolated WT1 peptide, (ii) a nucleic acid encoding the at least one WT1 peptide, and (iii) an immune cell comprising or presenting the at least one WT1 peptide or nucleic acid encoding the at least one WT1 peptide.
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公开(公告)号：EP4171621A1
公开(公告)日：2023-05-03
申请号：EP21832450.7
申请日：2021-06-28
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公开(公告)号：EP2968539A1
公开(公告)日：2016-01-20
申请号：EP14722878.7
申请日：2014-03-14
IPC分类号： A61K39/395 , A61K45/06 , A61K31/506 , A61K31/519 , A61P35/00 , A61P35/02
CPC分类号： C07K16/32 , A61K31/506 , A61K31/519 , A61K39/39558 , A61K45/06 , A61K2039/54 , A61K2039/545 , C07K16/3038 , A61K2300/00
摘要： In an attempt to improve primary disease responsiveness and/or to overcome resistant disease, the present disclosure provides a method for treating or inhibiting the proliferation of a WT-1 -dependent cancer comprising providing to a subject in need thereof a therapeutically effective amount of a tyrosine kinase inhibitor along with an anti-WT-1 /HLA antibody, that is, an antibody that specifically binds to a peptide of Wilms' tumor protein (WT-1 ) presented on the surface of the cancer cells in an HLA-restricted fashion.
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