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过继他T细胞治疗:不良反应和安全性控制

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发表于 2015-11-4 22:13:24 | 显示全部楼层 |阅读模式
httpwww.nature.comctijournalv3n6fullcti201411a.html


过继他T细胞治疗:不良反应和安全性控制

过继T细胞治疗在一定数量的恶性和感染性疾病中显示了潜在的完整和持续的不良反应。T细胞的改造持续性的进展,能够乐观的使得临床应用更加广泛。然而,更多的T细胞治疗需要考虑安全性问题,主要是靶向和非靶向毒性的发生,虽然不常出现,但是在一些场合下是必然会出现。在管理不良反应时,及时的药物干预是有效的,但是过继T细胞治疗会持续较长时间,伴随着一些不期望的副反应。最近证实的一个分子开关,能够诱导半胱天冬酶9iCASP9),具有这样的潜能来消除T细胞治疗带来的威胁,如果有需要,它能够消减移植的T细胞。在造血干细胞移植中,供体iCasp9修饰T细胞会因为移植物抗宿主病迅速消除。本文综述了现代T细胞疗法和开发的相关风险,以及iCasp9安全开关未来潜在的临床应用。







Adoptive T-cell therapy: adverse events and safety switches

The potential of adoptive T-cell therapy in effecting complete and durable responses has been demonstrated in a number of malignant and infectious diseases. Ongoing progress in T-cell engineering has given cause for optimism in the broader clinical applicability of this approach. However, the development of more potent T cells is checked by safety concerns, highlighted by the occurrence of on-target and off-target toxicities that, although uncommon, have been fatal on occasions. Timely pharmacological intervention is effective in the management of a majority of adverse events but adoptively transferred T cells can persist long term, along with any unwanted effects. A recently validated cellular safety switch, inducible caspase 9 (iCasp9), has the potential to mitigate the risks of T-cell therapy by enabling the elimination of transferred T cells if required.In haematopoietic stem cell transplantation, iCasp9-modified donor T cells can be rapidly eliminated in the event of graftversus-host disease. This review presents an overview of the risks associated with modern T-cell therapy and the development, clinical results and potential future application of the iCasp9 safety switch.
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