Chimeric antigen receptor (CAR)-T cell therapy possesses the potential to cause unexpected on-target toxicities that may be life-threatening. Non-human primates (NHPs) share considerable structural homology and expression profiles of most proteins with humans and are therefore utilised as an animal model for non-clinical safety studies. We have developed a lymphodepleted NHP model by conditioning the animals with immunosuppressive chemotherapy designed to simulate clinical practice conditions, to induce transient mixed chimerism before the administration of human CAR-T cells redirected to target Ephrin type-B receptor 4 (EPHB4-CAR-T cells) to evaluate the toxicity of these cells.

中文翻译：

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用于评估人嵌合抗原受体 T 细胞的急性靶向和肿瘤外毒性的去淋巴细胞非人灵长类动物模型

嵌合抗原受体 (CAR)-T 细胞疗法有可能导致意想不到的靶向毒性，可能危及生命。非人类灵长类动物 (NHP) 与人类的大多数蛋白质具有相当大的结构同源性和表达谱，因此被用作非临床安全性研究的动物模型。我们开发了一种清除淋巴的 NHP 模型，通过免疫抑制化疗对动物进行调节，旨在模拟临床实践条件，在施用重定向到靶向 Ephrin B 型受体 4 (EPHB4-CAR-T) 的人类 CAR-T 细胞之前诱导瞬时混合嵌合体细胞）来评估这些细胞的毒性。