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CAR-T细胞设计的理念

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发表于 2015-12-24 22:31:59 | 显示全部楼层 |阅读模式
Engineering CAR-T cells: Design concepts.
Abstract
Despite being empirically designed based on a simple understanding of TCR signaling, T cells engineered with chimeric antigen receptors (CARs) have been remarkably successful in treating patients with advanced refractory B cell malignancies. However, many challenges remain in improving the safety and efficacy of this therapy and extending it toward the treatment of epithelial cancers. Other aspects of TCR signaling beyond those directly provided by CD3ζ and CD28 phosphorylation strongly influence a T cell's ability to differentiate and acquire full effector functions. Here, we discuss how the principles of TCR recognition, including spatial constraints, Kon/Koff rates, and synapse formation, along with in-depth analysis of CAR signaling might be applied to develop safer and more effective synthetic tumor targeting receptors.
CAR-T细胞设计的理念
虽然依靠着对TCR信号的简单理解来设计,嵌合抗原受体修饰的T细胞已经能够成功的用于晚期恶性B淋巴细胞肿瘤的治疗。然而,这种技术在安全性和有效性方面的增强,仍然是面临着很多挑战,此外,将这种技术扩展到上皮癌的治疗中也面临着挑战。由CD3ζ和CD28 提供的TCR信号的其他方面强烈影响着T细胞分化和功能效应的获得。在本篇文章中,我们讨论了TCR识别的原理,包括空间的限制,Kon/Koff率,突触的形成,随着CAR信号的深入分析,可能被用于开发更安全和更有效的合成肿瘤靶向受体。
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