PDF(Pubmed)
Abstract：
Virus-specific T cells (VST) from partially-HLA matched donors have been effective for treatment of refractory viral infections in immunocompromised patients in prior studies with a good safety profile, but rare adverse events have been described. Here we describe a unique and severe adverse event of VST therapy in an infant with severe combined immunodeficiency, who receives, as part of a clinical trial (NCT03475212), third party VSTs for treating cytomegalovirus viremia following bone marrow transplantation. At one-month post-VST infusion, rejection of graft and reversal of chimerism is observed, as is an expansion of T cells exclusively from the VST donor. Single-cell gene expression and T cell receptor profiling demonstrate a narrow repertoire of predominantly activated CD4+ T cells in the recipient at the time of rejection, with the repertoire overlapping more with that of peripheral blood from VST donor than the infused VST product. This case thus demonstrates a rare but serious side effect of VST therapy.
摘要：
在先前的研究中，来自部分HLA匹配供体的病毒特异性T细胞（VST）可有效治疗免疫功能低下患者的难治性病毒感染，具有良好的安全性。但已经描述了罕见的不良事件。在这里，我们描述了患有严重联合免疫缺陷的婴儿的VST治疗的独特和严重的不良事件。谁收到，作为临床试验的一部分（NCT03475212），用于治疗骨髓移植后巨细胞病毒病毒血症的第三方VSTs。在VST输注后一个月,观察到移植物的排斥和嵌合状态的逆转，仅从VST供体扩增T细胞。单细胞基因表达和T细胞受体谱分析表明，在排斥反应时，受体中主要激活的CD4+T细胞的范围很窄。与输注的VST产品相比，该库与VST供体的外周血重叠更多。因此，这种情况表明了VST疗法的罕见但严重的副作用。
