Details

Autor(en) / Beteiligte

• Lu, You
• Xue, Jianxin
• Deng, Tao
• Zhou, Xiaojuan
• Yu, Kun
• Deng, Lei
• Huang, Meijuan
• Yi, Xin
• Liang, Maozhi
• Wang, Yu
• Shen, Haige
• Tong, Ruizhan
• Wang, Wenbo
• Li, Li
• Song, Jin
• Li, Jing
• Su, Xiaoxing
• Ding, Zhenyu
• Gong, Youling
• Zhu, Jiang
• Wang, Yongsheng
• Zou, Bingwen
• Zhang, Yan
• Li, Yanying
• Zhou, Lin
• Liu, Yongmei
• Yu, Min
• Wang, Yuqi
• Zhang, Xuanwei
• Yin, Limei
• Xia, Xuefeng
• Zeng, Yong
• Zhou, Qiao
• Ying, Binwu
• Chen, Chong
• Wei, Yuquan
• Li, Weimin
• Mok, Tony

Titel

Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer

Ist Teil von

• Nature medicine, 2020-05, Vol.26 (5), p.732-740

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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 (95% confidence interval, 6.9 to 8.5 weeks) and median overall survival was 42.6 weeks (95% confidence interval, 10.3-74.9 weeks). The median mutation frequency of off-target events was 0.05% (range, 0-0.25%) 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.