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 progre..... READ ARTICLE

Nature Medicine DOI:10.1038/s41591-020-0973-6

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