文章：

表达双特异性T细胞衔接器的过继转移T细胞在抗小鼠白血病中的活性增强

Improved anti-leukemia activities of adoptively transferred T cells expressing bispecific T-cell engager in mice

原文发布日期：2016-06-03

DOI: 10.1038/bcj.2016.38

类型: Original Article

开放获取: 是

英文摘要：

Despite the impressive clinical efficacy of T cells engineered to express chimeric antigen receptors (CAR-Ts), the current applications of CAR-T cell therapy are limited by major treatment-related toxicity. Thus, safer yet effective alternative approaches must be developed. In this study, we compared CD19 bispecific T-cell engager (BiTE)-transferred T cells that had been transfected by RNA electroporation with CD19 CAR RNA-transferred T cells both in vitro and in an aggressive Nalm6 leukemia mouse model. BiTEs were secreted from the transferred T cells and enabled both the transferred and bystander T cells to specifically recognize CD19+ cell lines, with increased tumor killing ability, prolonged functional persistence, increased cytokine production and potent proliferation compared with the CAR-T cells. More interestingly, in comparison with CD3/CD28 bead-stimulated T cells, T cells that were expanded by a rapid T-cell expansion protocol (REP) showed enhanced anti-tumor activities for both CAR and BiTE RNA-electroporated T cells both in vitro and in a Nalm6 mouse model (P<0.01). Furthermore, the REP T cells with BiTE RNAs showed greater efficacy in the Nalm6 leukemia model compared with REP T cells with CAR RNA (P<0.05) and resulted in complete leukemia remission.

摘要翻译： 

尽管表达嵌合抗原受体（CAR-T）的T细胞在临床上展现出显著疗效，但当前CAR-T细胞疗法的应用仍受到治疗相关严重毒性的限制。因此，必须开发更安全且有效的替代方案。本研究通过RNA电转技术，对比了CD19双特异性T细胞衔接器（BiTE）修饰的T细胞与CD19 CAR RNA修饰的T细胞在体外及侵袭性Nalm6白血病小鼠模型中的表现。BiTE可从修饰的T细胞中分泌，使经修饰的T细胞及旁观T细胞均能特异性识别CD19+细胞系，与CAR-T细胞相比，其肿瘤杀伤能力增强、功能持续性延长、细胞因子分泌增加且增殖能力显著提升。更有趣的是，与CD3/CD28磁珠刺激的T细胞相比，采用快速T细胞扩增方案（REP）扩增的T细胞，在体外及Nalm6小鼠模型中均显示出更强的抗肿瘤活性（P<0.01）。此外，在Nalm6白血病模型中，携带BiTE RNA的REP T细胞比携带CAR RNA的REP T细胞具有更优的疗效（P<0.05），并实现了白血病的完全缓解。

原文链接：

Improved anti-leukemia activities of adoptively transferred T cells expressing bispecific T-cell engager in mice