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    • 5. 发明公开
    • REGULATABLE CHIMERIC ANTIGEN RECEPTOR
    • 调节剂CHIMÄRER抗生素
    • EP3119425A1
    • 2017-01-25
    • EP15764851.0
    • 2015-03-13
    • Novartis AGThe Trustees of The University of PennsylvaniaEngels, Boris
    • ENGELS, BorisLOEW, AndreasMILONE, Michael C.ZHOU, Li
    • A61K39/00A61K38/00
    • Provided are compositions and methods relating to regulatable chimeric antigen receptors (RCARs), natural killer cell receptor CARs (NKR-CARs), and regulatable NKR-CARs (RNKR-CARs), where the intracellular signaling or proliferation of the RCAR or RNKR-CAR can be controlled to optimize the use of an RCAR/NKR-CAR- or RNKR-CAR-expressing cell to provide an immune response. Cells can be engineered to express a RNKR-CAR or to express a RCAR and a NKR-CAR (e.g., inhibitory NKR-CAR). For example, a RCAR or RNKR-CAR can comprise a dimerization switch that, upon the presence of a dimerization molecule, can couple an intracellular signaling domain to an extracellular recognition element, e.g., an antigen binding domain, an inhibitory counter ligand binding domain, or costimulatory ECD domain. An RCAR or RNKR-CAR can be engineered to include an appropriate antigen binding domain that is specific to a desired antigen target and used in the treatment of a disease.
    • 提供与可调节嵌合抗原受体(RCAR),天然杀伤细胞受体CAR(NKR-CAR)和可调节NKR-CAR(RNKR-CAR)有关的组合物和方法,其中RCAR或RNKR-CAR的细胞内信号传导或增殖 可以控制以优化RCAR / NKR-CAR或RNKR-CAR表达细胞的使用以提供免疫应答。 可以将细胞工程化以表达RNKR-CAR或表达RCAR和NKR-CAR(例如抑制性NKR-CAR)。 例如,RCAR或RNKR-CAR可以包含二聚转换开关,其在二聚化分子的存在下可以将细胞内信号结构域偶联到细胞外识别元件,例如抗原结合结构域,抑制性反配体结合结构域, 或共刺激ECD域。 RCAR或RNKR-CAR可以被设计成包括对所需抗原靶特异性并用于治疗疾病的合适的抗原结合结构域。