Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation
Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation
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DOI：
10.1182/blood-2013-02-486324
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发表时间：
2013-06-27
期刊：
影响因子：
20.3
通讯作者：
Heslop, Helen E.
中科院分区：
文献类型：
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作者：
Leen, Ann M.;Bollard, Catherine M.;Heslop, Helen E.
病毒特异性T细胞（VST）系可以提供有用的抗病毒预防和治疗的免疫缺陷患者，如果它是可能的，以避免产生一个单独的线为每个病人的必要性，往往在紧急的基础上。我们从具有常见HLA多态性的个体中制备了32个病毒特异性细胞系，这些个体对EB病毒（EBV）、巨细胞病毒或腺病毒具有免疫力。共有18个线管理的50例严重，难治性疾病，因为感染这些病毒之一造血干细胞移植后。输注后6周的完全或部分应答累积率为74.0%（95% CI，58.5%-89.5%），整个组（n = 50），73.9%巨细胞病毒（n = 23）、腺病毒（n = 18）和EBV（n = 9）分别为77.8%（95%CI，51.2%-96.6%）、66.7%（95%CI，36.9%-96.5%）。仅4例缓解者复发或进展。没有立即输注相关的不良事件，仅2例患者发生了新发移植物抗宿主病。尽管细胞系和受体之间存在差异，但VST的平均频率在输注后显著增加，与病毒DNA的显著减少和临床症状的消退一致。使用库存的第三方VST是快速治疗干细胞移植后严重或难治性病毒感染的可行且安全的方法。本研究在www.clinicaltrials.gov注册为NCT 00711035。
Virus-specific T cell (VST) lines could provide useful antiviral prophylaxis and treatment of immune-deficient patients if it were possible to avoid the necessity of generating a separate line for each patient, often on an emergency basis. We prepared a bank of 32 virus-specific lines from individuals with common HLA polymorphisms who were immune to Epstein-Barr virus (EBV), cytomegalovirus, or adenovirus. A total of 18 lines were administered to 50 patients with severe, refractory illness because of infection with one of these viruses after hematopoietic stem cell transplant. The cumulative rates of complete or partial responses at 6 weeks postinfusion were 74.0% (95% CI, 58.5%-89.5%) for the entire group (n = 50), 73.9% (95% CI, 51.2%-96.6%) for cytomegalovirus (n = 23), 77.8% for adenovirus (n = 18), and 66.7% (95% CI, 36.9%-96.5%) for EBV (n = 9). Only 4 responders had a recurrence or progression. There were no immediate infusion-elated adverse events, and de novo graft-versus-host disease developed in only 2 patients. Despite the disparity between the lines and their recipients, the mean frequency of VSTs increased significantly postinfusion, coincident with striking decreases in viral DNA and resolution of clinical symptoms. The use of banked third-party VSTs is a feasible and safe approach to rapidly treat severe or intractable viral infections after stem cell transplantation. This study is registered at www.clinicaltrials.gov as NCT00711035.