T cell immunotherapies have revolutionized treatment for a subset of cancers. Yet, a major hurdle has been the lack of facile and predicative preclinical animal models that permit dynamic visualization of T cell immune responses at single-cell resolution in vivo. Here, optically clear immunocompromised zebrafish were engrafted with fluorescent-labeled human cancers along with chimeric antigen receptor T (CAR T) cells, bispecific T cell engagers (BiTEs), and antibody peptide epitope conjugates (APECs), allowing real-time single-cell visualization of T cell–based immunotherapies in vivo. This work uncovered important differences in the kinetics of T cell infiltration, tumor cell engagement, and killing between these immunotherapies and established early endpoint analysis to predict therapy responses. We also established EGFR-targeted immunotherapies as a powerful approach to kill rhabdomyosarcoma muscle cancers, providing strong preclinical rationale for assessing a wider array of T cell immunotherapies in this disease.

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体内 T 细胞免疫治疗反应的单细胞成像

T 细胞免疫疗法已经彻底改变了一部分癌症的治疗方法。然而，一个主要障碍是缺乏简单且具有预测性的临床前动物模型，这些模型允许在体内以单细胞分辨率动态可视化 T 细胞免疫反应。在这里，光学透明的免疫受损斑马鱼被植入荧光标记的人类癌症以及嵌合抗原受体 T (CAR T) 细胞、双特异性 T 细胞接合剂 (BiTE) 和抗体肽表位缀合物 (APEC)，从而实现实时单细胞体内基于 T 细胞的免疫疗法的可视化。这项工作揭示了这些免疫疗法之间在 T 细胞浸润、肿瘤细胞参与和杀伤的动力学方面的重要差异，并建立了早期终点分析来预测治疗反应。