肿瘤细胞治疗研究
英文原题：Single-cell imaging of T cell immunotherapy responses in vivo.
T 细胞免疫疗法已经彻底改变了一部分癌症的治疗。
T细胞免疫疗法已彻底改变部分癌症的治疗，但目前缺乏简便且具有预测能力的临床前动物模型，难以在体内动态观察单细胞水平的T细胞免疫反应，这是该领域的一大障碍。本研究将荧光标记的人类癌细胞与CAR-T（CAR T）细胞、双特异性T细胞衔接器（BiTE）和抗体-肽表位偶联物（APEC）共同移植至光学透明的免疫缺陷斑马鱼体内，从而实时观察体内基于T细胞的免疫疗法，并达到单细胞分辨率。该模型揭示了不同疗法在T细胞浸润动力学、肿瘤细胞接触和杀伤方面的重要差异，并建立了可预测治疗应答的早期终点评估方法。研究还证实，靶向EGFR的免疫疗法能够有效杀伤横纹肌肉瘤肌源性癌细胞，为在该疾病中评估更多T细胞免疫疗法提供了有力的临床前依据。
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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