Bluestone Jeffrey A, Trotta Eleonora, Xu Daqi
University of California San Francisco, Diabetes Center , San Francisco, CA 94143 , USA +1 415 476 4451 ; jeff,
Expert Opin Ther Targets. 2015;19(8):1091-103. doi: 10.1517/14728222.2015.1037282. Epub 2015 Apr 16.
Immune tolerance remains the holy grail of therapeutic immunology in the fields of organ and tissue transplant rejection, autoimmune diseases, and allergy and asthma. We have learned that FoxP3(+)CD4(+) regulatory T cells play a vital role in both the induction and maintenance of self-tolerance.
In this opinion piece, we highlight regulatory T cells (Treg) cell biology and novel immune treatments to take advantage of these cells as potent therapeutics. We discuss the potential to utilize Treg and Treg-friendly therapies to replace current general immunosuppressives and induce tolerance as a path towards a drug-free existence without associated toxicities.
Finally, we opine on the fact that biomedicine sits on the cusp of a new revolution: the use of human cells as versatile therapeutic engines. We highlight the challenges and opportunities associated with the development of a foundational cellular engineering science that provides a systematic framework for safely and predictably regulating cellular behaviors. Although Treg therapy has become a legitimate clinical treatment, development of the therapy will require a better understanding of the underlying Treg biology, manufacturing advances to promote cost effectiveness and combinations with other drugs to alter the pathogenicity/regulatory balance.
在器官和组织移植排斥、自身免疫性疾病以及过敏和哮喘等领域,免疫耐受仍是治疗免疫学的圣杯。我们已经了解到,FoxP3(+)CD4(+)调节性T细胞在自身耐受的诱导和维持中都起着至关重要的作用。
在这篇观点文章中,我们重点介绍调节性T细胞(Treg)的细胞生物学以及利用这些细胞作为有效治疗手段的新型免疫疗法。我们讨论了利用Treg和对Treg友好的疗法来替代当前常规免疫抑制剂并诱导耐受的可能性,以此作为迈向无药物且无相关毒性状态的途径。
最后,我们认为生物医学正处于一场新革命的边缘:将人类细胞用作多功能治疗引擎。我们强调了与基础细胞工程科学发展相关的挑战和机遇,该科学为安全且可预测地调节细胞行为提供了一个系统框架。尽管Treg疗法已成为一种合理的临床治疗方法,但该疗法的发展需要更好地理解Treg的基础生物学,在制造方面取得进展以提高成本效益,并与其他药物联合使用以改变致病性/调节平衡。