RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy.
The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy.
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自然杀伤(NK)细胞是先天淋巴细胞,能够识别并清除感染细胞和转化细胞。NK 细胞在肿瘤监视中的重要性是 NK 细胞疗法作为癌症治疗方法发展的基础。NK-92 细胞系已被成功改造,以表达高亲和力 CD16 受体用于抗体依赖性细胞毒性,和/或表达嵌合抗原受体(CAR),后者能够识别肿瘤细胞表达的抗原并介导 NK 细胞活化。由于无需人类白细胞抗原配型或既往暴露于肿瘤抗原,NK-92 为开发下一代现货型细胞治疗平台提供了机会。经 CAR 工程改造的 NK-92 细胞在体外和体内临床前研究中均表现出强效抗肿瘤活性,推动了 CAR NK-92 细胞的临床开发。初步的 1 期数据表明,CAR NK-92 可以在临床上安全给药。在这篇综述中,我们概述了这种新型细胞免疫疗法在研究和临床应用方面的最新进展。
Natural killer (NK) cells are innate lymphocytes that recognize and clear infected and transformed cells. The importance of NK cells in tumor surveillance underlies the development of NK cell therapy as cancer treatment. The NK-92 cell line has been successfully modified to express high-affinity CD16 receptor for antibody-dependent cellular cytotoxicity and/or chimeric antigen receptors (CARs) that can recognize antigens expressed on tumor cells and mediate NK cell activation.
Since there is no need for human leukocyte antigen matching or prior exposure to the tumor antigens, NK-92 provides an opportunity for the development of next-generation off-the-shelf cell therapy platforms. CAR-engineered NK-92 cells have demonstrated robust antitumor activity in in vitro and in vivo preclinical studies, propelling the clinical development of CAR NK-92 cells.
Preliminary phase 1 data indicate that CAR NK-92 can be safely administered in the clinic. In this review, we provide an overview of recent advances in the research and clinical application of this novel cell immunotherapy.
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