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同种异体来源CAR-T细胞技术的挑战与机遇

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发表于 2015-12-20 22:39:06 | 显示全部楼层 |阅读模式
Challenges and opportunities of allogeneic donor-derived CAR T cells.
Abstract
PURPOSE OF REVIEW:
As T cells engineered with chimeric antigen receptors (CARs) are entering advanced phases of clinical trial testing with promising results, the potential implications of use in an allogeneic environment are emerging as an important consideration. This review discusses the use of allogeneic CAR therapy, the potential effects of T-cell receptor (TCR) signaling on CAR T-cell efficacy, and the potential for TCR elimination to generate an off-the-shelf product.

RECENT FINDINGS:
The majority of preclinical and clinical data regarding allogeneic T cells are focused on safety of their use given the potential for graft-versus-host disease (GVHD) mediated by the T-cell receptor expressed with the introduced CAR. Recent clinical trials using donor-derived CAR T cells are using either rigorous patient selection or T-cell selection (such as enrichment for virus-specific T cells). Although no GVHD has been reported, the efficacy of the allogeneic CAR treatment needs to be optimized. Several preclinical models limit allogeneic CAR-driven GVHD by utilizing memory T-cell selection, virus-specific T cells, gene-editing techniques, or suicide gene engineering.
SUMMARY:
In the allogeneic environment, the potential effects of TCR signaling on the efficacy of CAR could affect the clinical responses with the use of donor-derived CAR T cells. Better understanding of the functionality of donor-derived T cells for therapy is essential for the development of universal effector cells for CAR therapy.


同种异体来源CAR-T细胞技术的挑战与机遇
摘要
综述的目的
使用CARs修饰的T细胞技术正在进入临床试验的先进阶段,并且具有较好的前景,在异基因的环境中使用可能会出现的问题是目前需要考虑的事情。这篇综述讨论了异基因CAR-T细胞的使用,T细胞信号受体对CAR-T细胞的有效性的潜在作用,以及利用TCR的消除来生产产品的潜力。
最新的发现
临床前和临床数据对于同种异体T细胞研究大部分都集中在治疗的安全性,因为引入CAR会引起移植物抗宿主病(GVHD)。最新的临床试验使用的CAR-T细胞有严格的要求,例如严格的病人选择或者是T细胞选择(例如丰富的病毒特异性T细胞)。虽然没有报道产生GVHD,使用同种异体CAR-T细胞治疗的技术仍然需要优化。一些临床前模型利用选择中央记忆T细胞,病毒特异性T细胞,基因编辑技术,或自杀基因工程修改技术来限制同种异体CAR-T细胞诱导GVHD的发生,
总结:
在异体的环境中,TCR信号对CAR的潜在影响会通过使用捐赠来源的CAR-T细胞影响临床结果。更好的理解捐赠来源的T细胞的功能对CAR治疗技术的通用效应细胞的发展是非常必要的。



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