Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
Blood. 2010 Feb 4;115(5):925-35. doi: 10.1182/blood-2009-08-239186. Epub 2009 Oct 30.
T-cell immunotherapy that takes advantage of Epstein-Barr virus (EBV)-stimulated immunity has the potential to fill an important niche in targeted therapy for EBV-related cancers. To address questions of long-term efficacy, safety, and practicality, we studied 114 patients who had received infusions of EBV-specific cytotoxic T lymphocytes (CTLs) at 3 different centers to prevent or treat EBV(+) lymphoproliferative disease (LPD) arising after hematopoietic stem cell transplantation. Toxicity was minimal, consisting mainly of localized swelling at sites of responsive disease. None of the 101 patients who received CTL prophylaxis developed EBV(+) LPD, whereas 11 of 13 patients treated with CTLs for biopsy-proven or probable LPD achieved sustained complete remissions. The gene-marking component of this study enabled us to demonstrate the persistence of functional CTLs for up to 9 years. A preliminary analysis indicated that a patient-specific CTL line can be manufactured, tested, and infused for $6095, a cost that compares favorably with other modalities used in the treatment of LPD. We conclude that the CTL lines described here provide safe and effective prophylaxis or treatment for lymphoproliferative disease in transplantation recipients, and the manufacturing methodology is robust and can be transferred readily from one institution to another without loss of reproducibility.
利用 Epstein-Barr 病毒 (EBV) 刺激免疫的 T 细胞免疫疗法有可能成为 EBV 相关癌症靶向治疗的一个重要手段。为了研究长期疗效、安全性和实用性，我们研究了 114 名在 3 个不同中心接受 EBV 特异性细胞毒性 T 淋巴细胞 (CTL) 输注的患者，以预防或治疗造血干细胞移植后发生的 EBV(+)淋巴增殖性疾病 (LPD)。毒性极小，主要表现为反应性疾病部位的局部肿胀。101 名接受 CTL 预防治疗的患者中无一例发生 EBV(+)LPD，而 13 名接受 CTLs 治疗活检证实或可能 LPD 的患者中有 11 例获得持续完全缓解。本研究的基因标记部分使我们能够证明功能性 CTL 可维持长达 9 年。初步分析表明，可以为每位患者制造、测试和输注 CTL 线，费用为 6095 美元，与 LPD 治疗中使用的其他方法相比具有优势。我们得出结论，这里描述的 CTL 线为移植受者的淋巴增殖性疾病提供了安全有效的预防或治疗，并且制造方法稳健，可以从一个机构转移到另一个机构而不会失去可重复性。
