Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs) represent a promising treatment option for EBV-associated post-transplantation lymphoproliferative disorders (PTLD). However, production of EBV-CTLs is often complicated and expensive. In the present study, we sought to establish an easy-to-use and economical production protocol for EBV-CTLs. EBV-CTLs were generated using latent membrane protein 1 (LMP1) peptides based on a modified generation protocol of cytokine-induced killer (CIK) cells. After 2-week culture, cells were well expanded (median total cell number: 9.82 × 109; median expansion fold: 107.8) and the median EBV LMP1-specific CD8+ T cell number was 8.94 × 108 (median frequency: 6.7%). However, the EBV-CTL products, unlike CIK cells, did not exhibit NK-like anti-tumor activity. Furthermore, the clinical efficacy of EBV-CTLs was demonstrated with a successful treatment of PTLD on a compassionate use basis in a patient following haploidentical hematopoietic stem cell transplantation. This study indicates the safety and efficacy of EBV LMP1-specific CTLs generated based on a modified generation protocol of CIK cells. Further investigation in a well-designed clinical study is warranted.

中文翻译：

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LMP1特异性细胞毒性T细胞可用于治疗EBV相关的移植后淋巴细胞增生性疾病。

爱泼斯坦-巴尔病毒特异的细胞毒性T淋巴细胞（EBV-CTL）代表了与EBV相关的移植后淋巴细胞增生性疾病（PTLD）的有前途的治疗选择。但是，EBV-CTL的生产通常很复杂且昂贵。在本研究中，我们试图为EBV-CTL建立易于使用且经济的生产协议。EBV-CTL使用潜伏膜蛋白1（LMP1）肽根据细胞因子诱导的杀伤（CIK）细胞的改良生成方案生成。培养2周后，细胞扩增良好（中位数总细胞数：9.82×109；中位数扩增倍数：107.8），中值EBV LMP1特异性CD8 + T细胞数为8.94×108（中位数频率：6.7％）。但是，与CIK细胞不同，EBV-CTL产品没有表现出类似NK的抗肿瘤活性。此外，EBV-CTLs的临床疗效已通过在同性造血干细胞移植后以同情使用成功治疗PTLD的患者得到证明。这项研究表明基于改进的CIK细胞生成协议生成的EBV LMP1特异性CTL的安全性和有效性。必须对设计合理的临床研究进行进一步研究。