SCI
7 May 2020
Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer
Lu You,Xue Jianxin,Deng Tao et al. Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer.[J] .Nat. Med., 2020, undefined: undefined.
Clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 editing of immune checkpoint genes could improve the efficacy of T cell therapy, but the first necessary undertaking is to understand the safety and feasibility.
（CRISPR）–Cas9编辑免疫检查点基因可以提高T细胞疗法的疗效，但是首要的任务是了解安全性和可行性。
Here, we report results from a first-in-human phase I clinical trial of CRISPR–Cas9 PD-1-edited T cells in patients with advanced non-small-cell lung cancer (ClinicalTrials.gov NCT02793856). Primary endpoints were safety and feasibility, and the secondary endpoint was efficacy. The exploratory objectives included tracking of edited T cells. All prespecified endpoints were met.
在这里，我们报道了由CRISPR–Cas9 PD-1编辑的T细胞在晚期非小细胞肺癌患者中的一项首次人类I期临床试验结果（ClinicalTrials.gov NCT02793856）。主要终点是安全性和可行性，次要终点是功效。探索性目标包括跟踪编辑的T细胞。符合所有预定的终点。
PD-1-edited T cells were manufactured ex vivo by cotransfection using electroporation of Cas9 and single guide RNA plasmids. A total of 22 patients were enrolled; 17 had sufficient edited T cells for infusion, and 12 were able to receive treatment. All treatment-related adverse events were grade 1/2. Edited T cells were detectable in peripheral blood after infusion. The median progression-free survival was 7.7 weeks and median overall survival was 42.6 weeks.
使用Cas9和单向导RNA质粒的电穿孔，通过共转染离体生产PD-1编辑的T细胞。共有22例患者入选；17位编辑后的T细胞足以进行输液，而12位能够接受治疗。所有与治疗相关的不良事件均为1/2级。输注后在外周血中可检测到编辑过的T细胞。中位无进展生存期为7.7周，中位总生存期为42.6周。
The median mutation frequency of off-target events was 0.05% at 18 candidate sites by next generation sequencing. We conclude that clinical application of CRISPR–Cas9 gene-edited T cells is generally safe and feasible. Future trials should use superior gene editing approaches to improve therapeutic efficacy.
通过NGS，脱靶事件的中位突变频率在18个候选位点处为0.05％。我们得出结论，CRISPR–Cas9基因编辑的T细胞的临床应用通常是安全可行的。未来的试验应使用卓越的基因编辑方法来提高治疗效果。
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