Chimeric antigen receptor (CAR)‐T cell therapy redirected to specific antigens on tumor cells is a promising immunotherapy strategy for various cancers. Most target antigens are also expressed on normal tissues at varying levels, and therefore, a considerable challenge in the field is determining safety profiles, including life‐threatening off‐tumor and off‐target toxicities. The granulocyte–macrophage colony‐stimulating factor receptor (hGMR) is a promising target for CAR T‐cell therapy for a subset of acute myelocytic leukaemia, although it is also expressed on normal cells including monocytes, macrophages, CD34‐positive haematopoietic cells and vascular endothelial cells. hGMR and other immune‐related proteins are highly conserved between humans and cynomolgus macaques (Macaca fascicularis). Therefore, in this study, we engineered cynomolgus T cells to express CAR molecules redirected to hGMR by piggyBac (PB) transposon‐based gene transfer and adoptively transferred autologous hGMR‐CAR T cells into cynomolgus macaques.

中文翻译：

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自体非人灵长类动物模型用于对粒细胞-巨噬细胞集落刺激因子受体上 piggyBac 转座子介导的嵌合抗原受体 T 细胞的安全性评估

嵌合抗原受体 (CAR)-T 细胞疗法重定向到肿瘤细胞上的特定抗原是一种有前途的各种癌症的免疫治疗策略。大多数靶抗原也在正常组织上以不同水平表达，因此，该领域的一个相当大的挑战是确定安全性，包括危及生命的肿瘤外和脱靶毒性。粒细胞 - 巨噬细胞集落刺激因子受体 (hGMR) 是 CAR T 细胞治疗急性髓细胞性白血病亚组的有希望的靶点，尽管它也在正常细胞上表达，包括单核细胞、巨噬细胞、CD34 阳性造血细胞和血管内皮细胞。hGMR 和其他免疫相关蛋白在人和食蟹猴之间高度保守（Macaca fascicularis）。因此，在本研究中，我们设计了食蟹猴 T 细胞以表达通过piggyBac (PB) 转座子基因转移重定向到 hGMR 的 CAR 分子，并将自体 hGMR-CAR T 细胞过继转移到食蟹猴体内。