Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, The Methodist Hospital, Houston, TX 77030, USA.
Blood. 2013 Jun 27;121(26):5113-23. doi: 10.1182/blood-2013-02-486324. Epub 2013 Apr 22.
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-related 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.
病毒特异性 T 细胞(VST)系如果能够避免为每个患者分别生成单独的系,通常是在紧急情况下,那么为免疫缺陷患者提供有用的抗病毒预防和治疗将成为可能。我们从对 Epstein-Barr 病毒(EBV)、巨细胞病毒或腺病毒具有免疫力的具有常见 HLA 多态性的个体中制备了 32 个病毒特异性系的库。共有 18 条系被给予 50 名因造血干细胞移植后感染这些病毒之一而患有严重、难治性疾病的患者。在输注后 6 周时,完全或部分反应的累积率为整个组(n = 50)的 74.0%(95%CI,58.5%-89.5%),巨细胞病毒(n = 23)为 73.9%(95%CI,51.2%-96.6%),腺病毒为 77.8%(n = 18),EBV 为 66.7%(95%CI,36.9%-96.5%)(n = 9)。只有 4 名反应者出现复发或进展。没有立即与输注相关的不良事件,仅 2 名患者发生新的移植物抗宿主病。尽管系和其受者之间存在差异,但 VST 的平均频率在输注后显著增加,同时病毒 DNA 显著减少且临床症状得到缓解。使用第三方储存的 VST 是一种可行且安全的方法,可以在干细胞移植后迅速治疗严重或难治性病毒感染。这项研究在 www.clinicaltrials.gov 上注册为 NCT00711035。