Invention Grant
- Patent Title: Anti-WT1/HLA bi-specific antibody
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Application No.: US15034782Application Date: 2014-11-07
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Publication No.: US10239952B2Publication Date: 2019-03-26
- Inventor: David Scheinberg , Jingyi Xiang , Tao Dao , Su Yan , Cheng Liu
- Applicant: MEMORIAL SLOAN-KETTERING CANCER CENTER , EUREKA THERAPEUTICS, INC.
- Applicant Address: US NY New York US CA Emeryville
- Assignee: Memorial Sloan Kettering Cancer Center,Eureka Therapeutics, Inc.
- Current Assignee: Memorial Sloan Kettering Cancer Center,Eureka Therapeutics, Inc.
- Current Assignee Address: US NY New York US CA Emeryville
- Agency: Foley & Lardner LLP
- International Application: PCT/US2014/064621 WO 20141107
- International Announcement: WO2015/070061 WO 20150514
- Main IPC: A61K39/00
- IPC: A61K39/00 ; C07K16/32 ; C07K16/28

Abstract:
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.
Public/Granted literature
- US20160280796A1 ANTI-WT1/HLA BI-SPECIFIC ANTIBODY Public/Granted day:2016-09-29
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