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用于加速免疫疗法发现与转化的微系统技术。

Microsystem technologies for accelerating the discovery and translation of immunotherapies.

作者信息

Wang Zongjie, Liu Claire, Chen Kangfu, Song Joseph, Kelley Shana O

机构信息

Chan Zuckerberg Biohub Chicago, Chicago, IL, USA.

Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.

出版信息

Nat Rev Drug Discov. 2025 Sep 15. doi: 10.1038/s41573-025-01268-4.

Abstract

Immunotherapies have transformed the treatment of many cancers and autoimmune diseases. However, durable therapeutic benefits are achieved in only certain subsets of patients. Due to the complexity and heterogeneity of disease, it remains challenging to design effective immunotherapies and predict their effects. Microscale systems - including microfluidics, microelectronics and microscaffolds - are now being adapted to accelerate immunotherapy discovery and development, with the potential to address efficacy, toxicity, predictability and affordability challenges. These microsystems consist of miniaturized structures, sensors and actuators that can manipulate molecules and cells of the immune system with high accuracy and throughput. Advances facilitated by microsystem technologies relevant to the discovery and translation of key types of immunotherapy (monoclonal antibodies, cytokine-based drugs, engineered immune cells and therapeutic vaccines) include the development of high-throughput devices for functional selection, miniaturized bioreactors for biomanufacturing, engineered scaffolds for therapeutic administration and sensitive biosensors for immune surveillance post-administration. Challenges facing the clinical translation of microsystem-based immunotherapies include issues related to standardization and integration as well as the need for new regulatory guidance.

摘要

免疫疗法已经改变了许多癌症和自身免疫性疾病的治疗方式。然而,只有特定亚组的患者能获得持久的治疗益处。由于疾病的复杂性和异质性,设计有效的免疫疗法并预测其效果仍然具有挑战性。微尺度系统——包括微流体、微电子和微支架——目前正被用于加速免疫疗法的发现和开发,有望应对疗效、毒性、可预测性和可负担性等挑战。这些微系统由小型化的结构、传感器和致动器组成,能够高精度、高通量地操纵免疫系统的分子和细胞。微系统技术在关键类型免疫疗法(单克隆抗体、基于细胞因子的药物、工程免疫细胞和治疗性疫苗)的发现和转化方面取得的进展包括用于功能筛选的高通量设备的开发、用于生物制造的小型化生物反应器、用于治疗给药的工程支架以及用于给药后免疫监测的灵敏生物传感器。基于微系统的免疫疗法临床转化面临的挑战包括与标准化和整合相关的问题以及对新监管指南的需求。

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