Adoptive T-cell immunotherapy from third-party donors: characterization of donors and set up of a T-cell donor registry.
Adoptive T-cell immunotherapy from third-party donors: characterization of donors and set up of a T-cell donor registry.
复制标题
DOI：
10.3389/fimmu.2012.00410
复制
发表时间：
2012
影响因子：
7.3
通讯作者：
Blasczyk R
中科院分区：
文献类型：
--
作者：
Eiz-Vesper B;Maecker-Kolhoff B;Blasczyk R
人巨细胞病毒(CMV)、EB病毒(EBV)和腺病毒(ADV)感染和再激活是造血干细胞移植(HSCT)或实体器官移植(SOT)后免疫功能低下的受者常见的严重并发症。这些严重的不良事件与显著的发病率和死亡率有关。供者淋巴细胞输注(DLIS)通常用于治疗病毒感染和移植后白血病复发，但与潜在威胁生命的移植物抗宿主病(GvHD)有关。血清阳性供者来源的病毒特异性细胞毒效应T细胞(CTL)过继免疫治疗可迅速重建HSCT和器官移植后的抗病毒免疫。因此，它可以有效地预防这些病毒的临床表现，而没有明显的急性毒性或增加GvHD的风险。在接受异基因脐带血(CB)移植或病毒血清阴性捐赠者的移植的情况下，由于实体器官接受者通常无法获得捐赠者的血液，异基因第三方T细胞捐赠者将提供另一种选择。最近的研究表明，在粒细胞集落刺激因子(G-CSF)动员过程中，抗病毒记忆T细胞的功能活性长期受损。这一发现表明，即使是干细胞捐赠者也可能不是T细胞的最佳来源。在这种情况下，来自健康血清阳性个体的部分人类白细胞抗原(HLA)匹配的病毒特异性CTL可能是一个有希望的选择。因此，汉诺威医学院使用高通量T细胞分析方法对HLA型健康捐献者以及HSCT/SOT捐赠者的病毒特异性记忆T细胞进行了为期4年的频率评估。本章将讨论第三方T细胞捐献者登记的相关性和潜力，并将讨论其对过继T细胞免疫治疗的临床意义。
Infection with and reactivation of human cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (ADV) are frequent and severe complications in immunocompromised recipients after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT). These serious adverse events are associated with significant morbidity and mortality. Donor lymphocyte infusions (DLIs) are often used to treat both viral infections and leukemia relapses after transplantation but are associated with potentially life-threatening graft-versus-host disease (GvHD). Adoptive immunotherapy with virus-specific cytotoxic effector T cells (CTLs) derived from seropositive donors can rapidly reconstitute antiviral immunity after HSCT and organ transplantation. Therefore, it can effectively prevent the clinical manifestation of these viruses with no significant acute toxicity or increased risk of GvHD. In conditions, where patients receiving an allogeneic cord blood (CB) transplant or a transplant from a virus-seronegative donor and since donor blood is generally not available for solid organ recipients, allogeneic third party T-cell donors would offer an alternative option. Recent studies showed that during granulocyte colony-stimulating factor (G-CSF) mobilization, the functional activity of antiviral memory T cells is impaired for a long period. This finding suggests that even stem cell donors may not be the best source of T cells. Under these circumstances, partially human leukocyte antigen (HLA)-matched virus-specific CTLs from healthy seropositive individuals may be a promising option. Therefore, frequency assessments of virus-specific memory T cells in HLA-typed healthy donors as well as in HSCT/SOT donors using a high throughput T-cell assay were performed over a period of 4 years at Hannover Medical School. This chapter will address the relevance and potential of a third-party T-cell donor registry and will discuss its clinical implication for adoptive T-cell immunotherapy.