Allogeneic chimaeric antigen receptor T cells (allo-CAR T cells) derived from healthy donors could provide rapid access to standardized and affordable batches of therapeutic cells if their rejection by the host’s immune system is avoided. Here, by means of an in vivo genome-wide CRISPR knockout screen, we show that the deletion of Fas or B2m in allo- T cells increases their survival in immunocompetent mice. Human B2M^– allo-CAR T cells become highly sensitive to rejection mediated by natural killer (NK) cells, whereas FAS^– CAR T cells expressing normal levels of human leukocyte antigen I remain resistant to NK cells. CD3^– FAS^– CAR T cells outperformed CD3^– B2M^– CAR T cells in the control of leukaemia growth in mice under allogeneic pressure by T cells and NK cells. The partial protection of CD3^– FAS^– allo-CAR T cells from cellular rejection may improve the efficacy of allogeneic cellular therapies in patients with cancer.

如果避免了宿主免疫系统的排斥反应，来自健康供体的同种异体嵌合抗原受体 T 细胞（同种异体 CAR T 细胞）可以快速获得标准化且负担得起的治疗细胞批次。在这里，通过体内全基因组 CRISPR 敲除筛选，我们表明同种异体 T 细胞中 Fas 或 B2m 的缺失增加了它们在免疫功能正常小鼠中的存活率。人 B2M^– 同种异体 CAR T 细胞对自然杀伤 （NK） 细胞介导的排斥反应高度敏感，而表达正常水平人白细胞抗原 I 的 FAS^– CAR T 细胞对 NK 细胞保持耐药性。CD3-FAS-CAR T 细胞在 T 细胞和 NK 细胞同种异体压力下控制小鼠白血病生长方面优于 CD3-B2M-CAR T 细胞。 CD3-FAS-同种异体 CAR T 细胞对细胞排斥反应的部分保护可能会提高同种异体细胞疗法对癌症患者的疗效。