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ANTI-WT1/HLA BI-SPECIFIC ANTIBODY
专利权人:
发明人:
申请号:
HK17101702.8
公开号:
HK1227903A
申请日:
2017.02.16
申请国别(地区):
HK
年份:
2017
代理人:
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.La présente invention concerne une forme bispécifique dun anticorps monoclonal dun analogue des récepteurs des lymphocytes T présentant une réactivité contre un antigène des cellules effectrices humaines de limmunité et un peptide WT1/épitope HLA-A. Ledit anticorps se lie de façon sélective aux cellules leucémiques et tumorales solides exprimant WT1 et HLA-A, ainsi quaux lymphocytes T humains au repos activés afin de libérer de linterféron (IFN-γ) et de tuer les cellules cancéreuses cibles in vitro. Il est important de noter que lanticorps a été un médiateur de la prolifération des lymphocytes T autologues et a été à lorigine dune forte cytotoxicité à lencontre de cellules du cancer de lovaire fraîches. Lac
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