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结合型 CAR T 细胞:超越常规 CAR T 细胞的一步,为癌症免疫治疗带来新希望。

Conjugated CAR T cell one step beyond conventional CAR T cell for a promising cancer immunotherapy.

机构信息

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Cell Immunol. 2019 Nov;345:103963. doi: 10.1016/j.cellimm.2019.103963. Epub 2019 Aug 10.

Abstract

Cancer immunotherapy aims to enhance the immune system reactivity against tumour cells. Chimeric Antigen Receptor (CAR), presented on the surface of the T cells, specifically redirects the cell and demonstrates significant promises in treating patients with different types of haematologic malignancies. Although several cases of improvement have been reported, clinical experiences, such as excessive activity, poor control, toxicity and limited life span of conventional CAR T cells have emerged as treatment challenges associated with this therapeutic strategy. Recently, multiple switchable CAR T platforms have been made to enable better control in a dose-dependent manner, which is correlated to distinct characteristics of different switch molecules. This review aimed at a brief represention of toxicities of the CAR T cells, the obstacles facing tumour treatments especially in solid tumours, and finally providing a framework for classification of the newly developed Conjugated/Split CAR-T cell technologies to overcome difficulties. Overall, Newly developed Conjugated CAR T cells using among with soluble switch molecules seems to be as responsive as the conventional CAR T cells, yet providing many new useful options to effectively overcome limitations and significantly improve patient safety.

摘要

癌症免疫疗法旨在增强免疫系统对肿瘤细胞的反应性。嵌合抗原受体(CAR)存在于 T 细胞表面,可特异性重定向细胞,并在治疗不同类型血液恶性肿瘤患者方面显示出巨大的潜力。尽管已经报道了一些改善的病例,但临床经验表明,这种治疗策略存在与治疗相关的挑战,包括过度活性、难以控制、毒性和传统 CAR T 细胞寿命有限。最近,已经开发了多种可切换的 CAR T 平台,以实现剂量依赖性的更好控制,这与不同开关分子的独特特性相关。本综述旨在简要介绍 CAR T 细胞的毒性、肿瘤治疗特别是实体瘤治疗面临的障碍,并最终为分类新型连接/分裂 CAR-T 细胞技术提供框架,以克服困难。总的来说,使用可溶性开关分子的新型连接 CAR T 细胞似乎与传统的 CAR T 细胞一样具有反应性,但提供了许多新的有用选择,可有效克服限制并显著提高患者安全性。

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