决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
英文原题:Development of Genetically Engineered Feeder Cells for Natural Killer Cell Expansion.
Development of Genetically Engineered Feeder Cells for Natural Killer Cell Expansion.
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我们新开发的饲养层细胞可为 NK 细胞治疗提供有用的工具。
对 K562 细胞进行工程化改造,使其表达膜结合型白细胞介素-2(mbIL2)或白细胞介素-13(mbIL13)。
将从外周血单个核细胞(PBMC)中分离的人原代 NK 细胞与这些饲养细胞共同孵育后,活化 NK 细胞数量显著高于与亲本 K562 细胞共同培养的结果。荧光活化细胞分选(FACS)分析显示,使用 K562-mbIL2 或 K562-mbIL13 扩增的 NK 细胞表面富含 NKG2D 活化受体。与普通 K562 细胞培养的 NK 细胞相比,使用 K562-mbIL2 或 mbIL13 扩增的 NK 细胞杀伤癌细胞的能力更强。研究人员进一步使用与新型饲养细胞共同孵育的 NK 细胞制备抗 CD19 嵌合抗原受体(CAR)-NK 细胞;这些 CAR-NK 细胞对 CD19 阳性癌细胞系具有强效细胞毒作用。
新开发的饲养细胞可为 NK 细胞疗法提供有用工具。
K562 cells were engineered to express membrane bound interleukin-2 (mbIL2) or interleukin-13 (mbIL13).
The incubation of human primary NK cells isolated from peripheral blood mononuclear cells (PBMCs) with these feeder cells significantly increased the number of activated NK cells compared to K562 parental cells. Fluorescence-activated cell sorting (FACS) analysis demonstrated that NKG2D activating receptors were abundant on the surface of NK cells expanded by K562-mbIL2 or mbIL13 cells. NK cells expanded on K562-mbIL2 or mbIL13 lysed cancer cells more effectively than those cultured with normal K562 cells. Using NK cells incubated with our feeder cells, we developed anti-CD19 chimeric antigen receptor (CAR)-NK cells. They showed robust cytotoxic effect against CD19 positive cancer cell line.
Our newly developed feeder cells could provide useful tools for NK cell therapy.
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