捐赠者抗原特异性调节性T细胞给活体捐赠脏的接受者:A ONE研究联盟试点试验
Eva C Guinan1, Laura Contreras-Ruiz1, Kerry Crisalli2
1Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
概括
捐赠者抗原反应调节T细胞 (dar-Tregs) 在移植患者中显示出良好的安全性. 早期服用dar-Tregs可能会促进长期的移植存活,而不会发生排斥.
科学领域:
- 免疫学 免疫学 免疫学
- 移植医学 移植医学
- 临床试验 临床试验
背景情况:
- 调控性T细胞 (Tregs) 具有在临床前模型中证明的免疫抑制特性.
- 在自身免疫性疾病和移植的临床试验中正在研究Tregs.
- 一个研究联盟探索了Tregs在移植中的使用.
研究的目的:
- 评估活体捐赠者移植受体中捐赠者抗原反应Tregs (dar-Tregs) 的安全性和有效性.
- 为了评估移植后Tregs的免疫调节活性.
- 确定早期活检作为研究终点的潜力.
主要方法:
- 一个I-II期临床试验,涉及3名移植接受者.
- 移植后7至11天使用净化的dar-Tregs (CD4+CD25+CD127lo).
- 没有诱导治疗的修改免疫抑制疗法 (塔克罗利斯,甲酸莫菲蒂尔,类固醇).
主要成果:
- 在任何患者的协议活检中都没有观察到排斥事件.
- 在移植后11-13个月的所有患者中成功停止了mycophenolate mofetil.
- 在代移植和含有Treg的淋巴结合物中存在Treg积累的证据.
- 所有的患者在TACROLIMUS单一治疗>6年后都保持了优良的移植功能.
- 没有严重的不良事件归因于dar-Treg的管理.
结论:
- 当Dar-Tregs在移植后早期使用时,其安全性表现良好.
- 早期服用Tregs可能有助于持续的移植功能和避免排斥.
- 早期的活检发现和Treg存在表明潜在的免疫调节作用.
- 长期随访支持Tregs在移植耐受性方面的潜力.
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