先天免疫系统
免疫系统
生物
诱导多能干细胞
免疫学
免疫检查点
嵌合抗原受体
人类白细胞抗原
抗体
抗原
癌症研究
T细胞
免疫疗法
胚胎干细胞
遗传学
基因
作者
Alessia Gravina,Grigol Tediashvili,Yueting Zheng,Kumiko A. Iwabuchi,Sara M. Peyrot,Susan Z. Roodsari,Lucia Gargiulo,Shin Kaneko,Mitsujiro Osawa,Sonja Schrepfer,T. Deuse
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2023-11-01
卷期号:30 (11): 1538-1548.e4
标识
DOI:10.1016/j.stem.2023.10.003
摘要
Immune rejection of allogeneic cell therapeutics remains a major problem for immuno-oncology and regenerative medicine. Allogeneic cell products so far have inferior persistence and efficacy when compared with autologous alternatives. Engineering of hypoimmune cells may greatly improve their therapeutic benefit. We present a new class of agonistic immune checkpoint engagers that protect human leukocyte antigen (HLA)-depleted induced pluripotent stem cell-derived endothelial cells (iECs) from innate immune cells. Engagers with agonistic functionality to their inhibitory receptors TIM3 and SIRPα effectively protect engineered iECs from natural killer (NK) cell and macrophage killing. The SIRPα engager can be combined with truncated CD64 to generate fully immune evasive iECs capable of escaping allogeneic cellular and immunoglobulin G (IgG) antibody-mediated rejection. Synthetic immune checkpoint engagers have high target specificity and lack retrograde signaling in the engineered cells. This modular design allows for the exploitation of more inhibitory immune pathways for immune evasion and could contribute to the advancement of allogeneic cell therapeutics.
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