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公开(公告)号:US20230167191A1
公开(公告)日:2023-06-01
申请号:US17920724
申请日:2021-04-23
发明人: Henry Hongjun Ji , Runqiang Chen , Xiaomei Yuan
IPC分类号: C07K16/28 , C07K14/725 , C07K14/715 , C07K14/73 , C07K14/705 , A61K48/00 , A61K35/17
CPC分类号: C07K16/2896 , C07K14/7051 , C07K14/7155 , C07K14/70514 , C07K14/70521 , A61K48/005 , A61K35/17 , C07K2319/00 , A61K38/00
摘要: The present disclosure provides transgenic cells that express memory dimeric antigen receptors (mDARs), where the mDAR constructs comprise a JAK-STAT intracellular region having a cytokine receptor intracellular region which includes Box 1 and Box 2 motifs for binding a Janus kinase (JAK) which can play a role in JAK-STAT cellular signaling pathway to induce effector cell activation and proliferation. In one embodiment, the JAK-STAT intracellular region further comprises a CD3zeta intracellular signaling region having an intact ITAM region, or having ITAM 1 and 3, or having only ITAM 3 with a partial deletion. Transgenic cells expressing the mDAR constructs exhibit potent cytotoxicity, and release reduced levels of cytokines, compared to traditional DARs that lack a cytokine receptor intracellular region. The mDAR constructs have antibody-like properties as they bind specifically to a target antigen. Transgenic cells expressing the mDAR constructs can be used for directed cell therapy.