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T CELL MODIFIED WITH A SYNTHETIC RECEPTOR CONTAINING A SINGLE ITAM SIGNALING MOTIF

机译:T细胞用含有单个ITAM信号传导基序的合成受体进行修饰

摘要

The present invention refers to a αβ T cell genetically modified to express a recombinant chimeric antigen receptor (CAR), wherein the recombinant CAR comprises (a) an extracellular domain comprising an antigen binding region, (b) a transmembrane domain, (c) a co-stimulatory signaling domain, and (d) an intracellular signaling domain, wherein the extracellular domain comprises the extracellular domain of an NKG2D receptor, and wherein the intracellular signaling domain comprises one immunoreceptor tyrosine-based activation motif (ITAM); the recombinant CAR used to modify the αβ T cell; a pharmaceutical composition comprising the genetically modified αβ T cell; method of treating cancer or tumor using the genetically modified αβΤ cell; and method of preparing the genetically modified αβ T cell. In one embodiment, the genetically modified αβΤ cell comprises a CAR comprising the extracellular domain of NKG2D receptor, an lgG4 hinge region, a CD28 transmembrane domain, a 4-1 BB co-stimulatory signaling domain and a single ITAM-containing DAP 12 domain.
机译:本发明涉及遗传修饰的αβT细胞以表达重组嵌合抗原受体(轿厢),其中重组载体包含(a)包含抗原结合区域,(b)跨膜结构域的细胞外结构域,(c)a共刺激信号域,和(d)细胞内信号域,其中细胞外结构域包括NKG2D受体的细胞外结构域,其中细胞内信号结构域包含一种免疫受体酪氨酸的活化基序(ITAM);用于改变αβT细胞的重组型汽车;药物组合物,其包含遗传改性的AβT细胞;使用遗传修饰的αβτ细胞治疗癌症或肿瘤的方法;和制备遗传修饰的αβT细胞的方法。在一个实施方案中,遗传修饰的αβτ细胞包括包括NKG2D受体的细胞外结构域,LGG4铰链区域,CD28跨膜结构域,4-1BB共刺激信号域,4-1BB共刺激信号域和含有单个ITAM的DAP 12结构域的载体。

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