当前位置:科学网首页 > 小柯机器人 >详情
突触调节的CAR增强免疫细胞抗肿瘤活性
作者:小柯机器人 发布时间:2023/2/6 9:05:24


美国圣裘德儿童研究医院Peter J. Chockley等研究人员发现,突触调节的嵌合抗原受体(CAR)增强免疫细胞抗肿瘤活性。这一研究成果于2023年2月2日在线发表在国际学术期刊《自然—生物技术》上。

研究人员试图通过在CAR上添加细胞内支架蛋白结合位点来调节CAR免疫突触。研究人员人员使用PDZ结合模体(PDZbm),从而使得额外的脚手架交联增强突触形成和自然杀伤细胞(NK)CAR细胞极化。这种CAR设计的联合效应导致在体外和体内效应细胞功能的增加。此外,研究人员使用了T细胞,并观察到效应子功能的类似整体增强。在包括实体瘤在内的许多不同肿瘤模型中,突触调节的CAR免疫细胞表现出增强的突触强度、分泌细胞因子的数量和丰度,增强对肿瘤细胞的杀伤并延长生存期。

据悉,CAR技术已被临床应用于恶性血液病的治疗;然而,实体瘤对CAR疗法仍有抵抗。NK由于其固有的抗肿瘤功能,可能为CAR方法提供了一种最佳的免疫细胞类别。

附:英文原文

Title: Synapse-tuned CARs enhance immune cell anti-tumor activity

Author: Chockley, Peter J., Ibanez-Vega, Jorge, Krenciute, Giedre, Talbot, Lindsay J., Gottschalk, Stephen

Issue&Volume: 2023-02-02

Abstract: Chimeric antigen receptor (CAR) technologies have been clinically implemented for the treatment of hematological malignancies; however, solid tumors remain resilient to CAR therapeutics. Natural killer (NK) cells may provide an optimal class of immune cells for CAR-based approaches due to their inherent anti-tumor functionality. In this study, we sought to tune CAR immune synapses by adding an intracellular scaffolding protein binding site to the CAR. We employ a PDZ binding motif (PDZbm) that enables additional scaffolding crosslinks that enhance synapse formation and NK CAR cell polarization. Combined effects of this CAR design result in increased effector cell functionality in vitro and in vivo. Additionally, we used T cells and observed similar global enhancements in effector function. Synapse-tuned CAR immune cells exhibit amplified synaptic strength, number and abundance of secreted cytokines, enhanced killing of tumor cells and prolonged survival in numerous different tumor models, including solid tumors.

DOI: 10.1038/s41587-022-01650-2

Source: https://www.nature.com/articles/s41587-022-01650-2

期刊信息

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:68.164
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex