Single-cell imaging of T cell immunotherapy responses in vivo.
Single-cell imaging of T cell immunotherapy responses in vivo.
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DOI：
10.1084/jem.20210314
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发表时间：
2021-10-04
期刊：
影响因子：
--
通讯作者：
Langenau DM
中科院分区：
文献类型：
--
作者：
Yan C;Yang Q;Zhang S;Millar DG;Alpert EJ;Do D;Veloso A;Brunson DC;Drapkin BJ;Stanzione M;Scarfò I;Moore JC;Iyer S;Qin Q;Wei Y;McCarthy KM;Rawls JF;Dyson NJ;Cobbold M;Maus MV;Langenau DM
使用rag 2 Δ/Δ，il 2 rga −/−斑马鱼的异种移植癌症研究允许通过CAR T细胞，BiTE和APEC免疫疗法对T细胞介导的肿瘤杀伤进行简单的单细胞成像，并确定EGFR靶向免疫疗法作为横纹肌肉瘤肌肉癌症的有效治疗。T细胞免疫疗法彻底改变了一部分癌症的治疗方法。然而，一个主要的障碍是缺乏简单的和预测性的临床前动物模型，允许在体内以单细胞分辨率动态可视化T细胞免疫应答。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沿着嵌合抗原受体T（CAR T）细胞、双特异性T细胞嵌合体（BiTE）和抗体肽表位缀合物（APEC），允许基于T细胞的免疫疗法在体内的实时单细胞可视化。这项工作揭示了这些免疫疗法之间T细胞浸润，肿瘤细胞参与和杀伤动力学的重要差异，并建立了早期终点分析以预测治疗反应。我们还建立了EGFR靶向免疫疗法作为杀死横纹肌肉瘤肌肉癌的有力方法，为评估这种疾病中更广泛的T细胞免疫疗法提供了强有力的临床前理论基础。
Xenograft cancer studies using rag2Δ/Δ, il2rga−/− zebrafish allow facile, single-cell imaging of T cell–mediated tumor killing by CAR T cell, BiTE, and APEC immunotherapies and identified EGFR-targeted immunotherapies as an effective treatment for rhabdomyosarcoma muscle cancers. 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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DOI：
10.1158/1078-0432.ccr-18-0432
发表时间：
2019-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Majzner RG;Theruvath JL;Nellan A;Heitzeneder S;Cui Y;Mount CW;Rietberg SP;Linde MH;Xu P;Rota C;Sotillo E;Labanieh L;Lee DW;Orentas RJ;Dimitrov DS;Zhu Z;Croix BS;Delaidelli A;Sekunova A;Bonvini E;Mitra SS;Quezado MM;Majeti R;Monje M;Sorensen PHB;Maris JM;Mackall CL
通讯作者：
Mackall CL
DOI：
10.1084/jem.20061890
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Boissonnas A;Fetler L;Zeelenberg IS;Hugues S;Amigorena S
通讯作者：
Amigorena S
影响因子：
3.6
作者：
Brischwein, K;Schlereth, B;Baeuerle, PA
通讯作者：
Baeuerle, PA
影响因子：
16.6
作者：
Hegde, Meenakshi;Joseph, Sujith K.;Ahmed, Nabil
通讯作者：
Ahmed, Nabil
影响因子：
20.3
作者：
Fraietta, Joseph A.;Beckwith, Kyle A.;Maus, Marcela V.
通讯作者：
Maus, Marcela V.