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直接重编程的 NK 细胞用于癌症免疫治疗

英文原题:Directly reprogrammed natural killer cells for cancer immunotherapy.

查看英文原题

Directly reprogrammed natural killer cells for cancer immunotherapy.

PubMed 2021/08/02(内容时间) Nat Biomed Eng Q1 · IF 26.3(JCR 2025)

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中文摘要

有效且易获取的自然杀伤(NK)细胞来源将拓宽其作为免疫治疗药物的应用,特别是用于实体癌。在此,我们展示,使用多能性转录因子和优化的重编程培养基,可以将人类体细胞直接重编程为具有 CD56 bright CD16 bright 表型的 NK 细胞。直接重编程的 NK 细胞具有强大的固有-适应性免疫调节活性,并对广泛的癌细胞(包括难以治疗的实体癌和癌症干细胞)具有高度效力。携带癌症特异性嵌合抗原受体的直接重编程 NK 细胞,以及与能够介导抗体依赖性细胞介导的细胞毒作用的抗体联合使用的重编程 NK 细胞,均产生了选择性抗癌效果,且效力增强。将人类体细胞直接重编程为 NK 细胞,适合用于自体 and 异体 NK 细胞的生产,并将促进癌症免疫疗法和联合疗法的设计与测试。

展开英文摘要原文

Efficacious and accessible sources of natural killer (NK) cells would widen their use as immunotherapeutics, particularly for solid cancers.

Here, we show that human somatic cells can be directly reprogrammed into NK cells with a CD56 bright CD16 bright phenotype using pluripotency transcription factors and an optimized reprogramming medium. The directly reprogrammed NK cells have strong innate-adaptive immunomodulatory activity and are highly potent against a wide range of cancer cells, including difficult-to-treat solid cancers and cancer stem cells.

Both directly reprogrammed NK cells bearing a cancer-specific chimeric antigen receptor and reprogrammed NK cells in combination with antibodies competent for antibody-dependent cell-mediated cytotoxicity led to selective anticancer effects with augmented potency. The direct reprogramming of human somatic cells into NK cells is amenable to the production of autologous and allogeneic NK cells, and will facilitate the design and testing of cancer immunotherapies and combination therapies.

论文信息

作者
Kim HS、Kim JY、Seol B、Song CL、Jeong JE、Cho YS
第一作者单位
Stem Cell Research Laboratory, Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.South Korea
通讯作者单位
Stem Cell Research Laboratory, Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. june@kribb.re.kr.South Korea
文献类型
非美国政府资助研究
期刊
Nature biomedical engineering2021 Nov
原文标识
PubMed 34341536 · DOI 10.1038/s41551-021-00768-z