Virus-specific T-cell banks for 'off the shelf' adoptive therapy of refractory infections.
Virus-specific T-cell banks for 'off the shelf' adoptive therapy of refractory infections.
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DOI：
10.1038/bmt.2016.17
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发表时间：
2016-09
影响因子：
4.8
通讯作者：
Doubrovina E
中科院分区：
文献类型：
--
作者：
O'Reilly RJ;Prockop S;Hasan AN;Koehne G;Doubrovina E
使用移植供体来源的病毒特异性 T 细胞进行过继免疫疗法已成为治疗药物难治性 EBV+ 淋巴瘤以及异基因造血细胞移植复杂化的 CMV 和腺病毒感染的潜在治疗方法。来自健康第三方捐赠者的 HLA 部分匹配的病毒特异性 T 细胞的过继转移也显示出治疗这些疾病的前景，疾病反应率为 50-76%，并且在初步试验中记录的毒性或 GVHD 发生率极低。在这篇综述中，我们研究了移植供体和第三方供体衍生的病毒特异性 T 细胞的报道经验，确定了导致治疗反应或失败的病毒病原体、施用的 T 细胞和患病宿主的特征。我们还描述了我们中心库中病毒特异性 T 细胞系的特征，以及体外培养促进特异表位的免疫显性 T 细胞扩增的频率，这些表位由有限的 HLA 等位基因呈现，这些等位基因非常普遍，这有利于其广泛的治疗适用性。
Adoptive immunotherapy with transplant donor-derived virus-specific T-cells has emerged as a potentially curative approach for the treatment of drug refractory EBV+lymphomas as well as CMV and adenovirus infections complicating allogeneic hematopoietic cell transplants. Adoptive transfer of HLA partially matched virus-specific T-cells from healthy third party donors has also shown promise in the treatment of these conditions, with disease response rates of 50–76% and strikingly low incidences of toxicity or GVHD recorded in initial trials. In this review, we examine the reported experience with transplant donor and third party donor-derived virus specific T-cells, identifying characteristics of the viral pathogen, the T-cells administered and the diseased host that contribute to treatment response or failure. We also describe the characteristics of virus-specific T-cell lines in our center’s bank and the frequency with which in vitro culture promotes expansion of immunodominant T-cells specific for epitopes that are presented by a limited array of HLA alleles that are highly prevalent which facilitates their broad applicability for treatment.