Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease.

Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease.
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良好的制造实践实践的同种异体爱泼斯坦 - 巴尔病毒(EBV)特异性细胞毒性细胞库的建立和运行,用于治疗与EBV相关的淋巴增生性疾病。

DOI:
10.1111/bjh.13051
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发表时间:
2014-11
影响因子:
6.5
通讯作者:
Turner ML
Turner ML
中科院分区:
医学2区
文献类型:
--
作者:
Vickers MA;Wilkie GM;Robinson N;Rivera N;Haque T;Crawford DH;Barry J;Fraser N;Turner DM;Robertson V;Dyer P;Flanagan P;Newlands HR;Campbell J;Turner ML

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EB病毒(EBV)与多种恶性肿瘤有关,包括移植后淋巴增生性疾病(PTLD)。PTLD的传统治疗方法通常是成功的,但存在器官排斥反应的风险,并会产生显著的副作用。从外周血淋巴细胞体外产生的EBV特异性细胞毒性T淋巴细胞(CTL)提供了一种副作用小的替代治疗方式,但自体CTL很难用于临床实践。在这里,我们报告了来自25名献血者的EBV特异性CTL的建立和运作,这些献血者的人类白细胞抗原(HLA)型在欧洲人群中被发现的频率很高。自获得执照以来,已有37名患者与这些捐赠者分享了3个I类和2个II类HLA型的中位数。已经为10名淋巴增生性疾病患者注入了细胞,其中8人获得了完全缓解。两例难治性疾病患者的人类白细胞抗原II类均不匹配。两例接受细胞的EBV相关非造血肉瘤均未达到完全缓解。13名患者在可以发放任何细胞之前死亡,强调应该在患者成为前终端之前与银行联系。因此,这种第三方供者来源的EBV特异性CTL细胞库可以为大多数患者提供合适的匹配细胞,大多数受者都有良好的结果。
Epstein-Barr virus (EBV) is associated with several malignancies, including post-transplant lymphoproliferative disorder (PTLD). Conventional treatments for PTLD are often successful, but risk organ rejection and cause significant side effects. EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from peripheral blood lymphocytes provide an alternative treatment modality with few side effects, but autologous CTLs are difficult to use in clinical practice. Here we report the establishment and operation of a bank of EBV-specific CTLs derived from 25 blood donors with human leucocyte antigen (HLA) types found at high frequency in European populations. Since licensure, there have been enquiries about 37 patients, who shared a median of three class I and two class II HLA types with these donors. Cells have been infused into ten patients with lymphoproliferative disease, eight of whom achieved complete remission. Neither patient with refractory disease was matched for HLA class II. Both cases of EBV-associated non-haematopoietic sarcoma receiving cells failed to achieve complete remission. Thirteen patients died before any cells could be issued, emphasizing that the bank should be contacted before patients become pre-terminal. Thus, this third party donor-derived EBV-specific CTL cell bank can supply most patients with appropriately matched cells and most recipients have good outcomes.
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