Advances in modular control of CAR-T therapy with adapter-mediated CARs.

Advances in modular control of CAR-T therapy with adapter-mediated CARs.
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DOI:
10.1016/j.addr.2022.114358
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发表时间:
2022-08
影响因子:
16.1
通讯作者:
--
中科院分区:
医学1区
文献类型:
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蛋白质工程为T细胞免疫治疗领域的成功做出了贡献,包括嵌合抗原受体(CAR) T细胞治疗。CAR - T细胞疗法已成为癌症免疫治疗的支柱,通过靶向B细胞抗原CD19,证明了对B细胞恶性肿瘤的临床有效性。目前的基因编辑技术对CAR - T细胞活性的安全控制有限,这给控制患者体内的CAR - T细胞带来了障碍。或者,CAR - T细胞的活性可以通过工程CAR结合可溶的适配器分子来控制,这些适配器分子可以指导CAR - T细胞和靶细胞之间的相互作用。这种适配器介导方法的灵活性克服了传统CAR - T细胞的刚性特异性,允许靶向多种细胞类型。在这里,我们描述了适配CAR - T技术,以及这些方法如何强调蛋白质工程在T细胞治疗的可编程工具设计中的日益重要的作用。
Protein engineering has contributed to successes in the field of T cell-based immunotherapy, including chimeric antigen receptor (CAR) T cell therapy. CAR T cell therapy has become a pillar of cancer immunotherapy, demonstrating clinical effectiveness against B cell malignancies by targeting the B cell antigen CD19. Current gene editing techniques have limited safety controls over CAR T cell activity, which presents a hurdle for control of CAR T cells in patients. Alternatively, CAR T cell activity can be controlled by engineering CARs to bind soluble adapter molecules that direct the interaction between the CAR T cell and target cell. The flexibility in this adapter-mediated approach overcomes the rigid specificity of traditional CAR T cells to allow targeting of multiple cell types. Here we describe adapter CAR T technologies and how these methods emphasize the growing role of protein engineering in the design of programmable tools for T cell therapies.
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