嵌合抗原受体(Cars)的未来:它能推动癌症以外的解决方案吗?自身免疫性疾病的例子

Español Marta, M. Berta, Llobell Arturo, C. María, Boronat Anna
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引用次数: 4

摘要

中华免疫学杂志,2017,5(3):00158载体。在收集t细胞(通常来自患者的血液)后,通过引入CAR并诱导其在t细胞表面的表达对其进行体外修饰。在扩增这些CAR+ t细胞后,这些细胞被注入患者的血液中,以产生针对肿瘤的特异性免疫反应。CART细胞通过单链可变片段scFv (single-chain variable fragment,单链可变片段)的特异性来检测肿瘤细胞表面的抗原,然后杀死它们,从而能够识别癌细胞[2,3]。CAR与其配体相互作用的亲和力和亲和度高于T细胞受体(TCR)与其肽- mhc配体的相互作用;然而,CAR(而不是tcr)不能识别细胞内分子[4]。CAR由scFv序列、跨膜区和(通常至少两个)激活t细胞的结构域(如CD3、CD28和/或CD137[5]的信号传导结构域)的组合组成。尽管大多数临床试验集中在难治性B细胞淋巴增生疾病,CAR策略也依赖于实体肿瘤。在任何情况下,car的应用并不局限于癌症治疗。各种car已被用于治疗不同的病理,如病毒或真菌感染b[6]和自身免疫性疾病,本文综述了主要方面。
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Future of Chimeric Antigen Receptors (Cars): Could it Drive Solutions Beyond Cancer? Examples in Autoimmune Diseases
MOJ Immunol 2017, 5(3): 00158 vector). After collecting T-cells, usually from patient’s blood (leukoapheresis), they are ex-vivo modified by introducing CAR and by inducing its expression on the T-cell surface. After expanding these CAR+ T-cells, these cells are infused in the bloodstream of the patient to generate a specific immune response against tumour. CART cells become able to recognize cancerous cells through the specificity of a scFv (single-chain variable fragment) to detect an antigen on the surface of the tumour cells, and after that to kill them [2,3]. The affinity and the avidity of the interaction between a CAR and its ligand are higher than the interaction between T cell receptor (TCR) and its peptide-MHC ligand; however, a CAR (instead of TCRs) is unable to recognize intracellular molecules [4]. CAR consists of the combination of a scFv sequence, a transmembrane region and (usually at least two) domains activating for T-cells, such as signalling domains of CD3, CD28 and/or CD137 [5]. Although most of clinical trials are focused on refractory B cell lymphoprolipherative disorders, the CAR strategy is also being relied upon solid tumours. In any case the employment of CARs is not restricted to cancer therapy. A variety of CARs have been used to treat different pathologies such as viral or fungal infections [6] and autoimmune diseases, the main aspect reviewed in this article.
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