嵌合抗原受体
免疫系统
诱导多能干细胞
抗原
基因组编辑
CD19
免疫疗法
生物
遗传增强
癌症研究
免疫学
基因
清脆的
遗传学
胚胎干细胞
作者
Stefanie R. Bailey,Marcela V. Maus
标识
DOI:10.1038/s41587-019-0137-8
摘要
Autologous T cells that have been genetically modified to express a chimeric antigen receptor (CAR) targeting the B cell antigen CD19 have yielded remarkable clinical responses in patients with B cell malignancies, and are now on the market as anticancer ‘drugs’. Riding on this success, the field of immune cell engineering is rapidly growing, with creative solutions to major outstanding challenges, such as limitations in target antigen selection, the hostility of the tumor microenvironment and the logistical challenges of generating autologous therapies. Innovations in antigen receptor design, coupled with advances in gene transfer and gene-editing technologies, have enabled the engineering of T cells to have sophisticated sensing circuits, to have synthetic functionalities, and to be used as off-the-shelf, universal cellular products. As these technologies are applied to other immune cells, such as natural killer cells, hematopoietic cells or induced pluripotent stem cells, the potential to transform the treatment of many cancers, as well as other diseases, is palpably exciting. We discuss the pipeline of several influential innovations in the preclinical setting, the early translational results from clinical trials of these next-generation approaches, and the outlook for gene-modified or gene-edited cell therapies. Bailey and Maus discuss cutting-edge developments in engineering immune cells towards expanding the reach and efficacy of adoptive cell therapies in cancer and beyond.
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