On April 27, 2020, Prof. Lu You's team from the Department of Thoracic Oncology of West China Hospital (WCH) published the research results of "Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer" online in Nature Medicine (IF: 30.641). The safety and feasibility of this therapy in NSCLC were first demonstrated by editing the PD-1 gene in T cells in vitro via CRISPR-Cas9 editing technology, then amplifying by in vitro T cell culture, and then re-infusing into the subjects with non-small cell lung cancer (NSCLC). The first author& corresponding author is Prof. Lu You from the Department of Thoracic Oncology of WCH, and the other co-first authors are Xue Jianxin, a researcher in the Department of Thoracic Oncology, and Zhou Xiaojuan, an attending physician. WCH is the first institute. 

According to the first report of Nature in July 2016, Prof. Lu You's team planned to carry out the first-in-human clinical trial of CRISPR-Cas9 gene editing, and performed the first subject treatment in October 2016. The project team followed up for 2 years in strict accordance with the clinical study protocol, with the deadline set on January 31, 2020. In this clinical trial, gene-edited cell therapy was completed in 12 patients with advanced lung cancer who failed third-line or above treatment, and the enrolled subjects were safe and well tolerated. No grade 3 or above cell therapy-related toxicity or treatment-related death occurred. Of the 12 subjects, median progression-free survival (PFS) was 7.7 weeks and median overall survival (OS) was 42.6 weeks. Of the two subjects with clinically evaluated stable disease (SD), one subject had been stable for approximately 18 months. 

The clinical trial also focused on the off-target effects of CRISPR-mediated gene editing on T cell products, and the team used next generation sequencing technology (NGS) and whole genome sequencing technology (WGS) for off-target analysis of cell products, respectively. The results showed that the off-target effects resulting from CRISPR-mediated gene editing were low in mutation frequency or unfrequent.

This clinical study is involved with a translational phase I clinical trial, and the publicized results provide an important basis for further translation of CRISPR-mediated gene editing into clinical research.