将雏鸡胚胎绒毛膜作为评估嵌合抗原受体 T 细胞疗法对实体瘤体内疗效的平台

Q3 Medicine
Allison J Nipper, Emilie A K Warren, Kershena S Liao, Hsuan-Chen Liu, Chieko Michikawa, Caroline E Porter, Gabrielle A Wells, Mariana Villanueva, Fabio Henrique Brasil da Costa, Ratna Veeramachaneni, Hugo Villanueva, Masataka Suzuki, Andrew G Sikora
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引用次数: 0

摘要

受精卵绒毛膜(CAM)是滋养发育中胚胎的一层高血管化膜,它也支持移植细胞和肿瘤外植体快速生长出三维血管化肿瘤。由于小鼠异种移植模型受到时间、成本和可扩展性的限制,我们建议将CAM肿瘤作为一种快速、高效的筛选工具,用于评估嵌合Ag受体(CAR)T细胞对实体瘤的抗肿瘤疗效。我们测试了人表皮生长因子受体 2(HER2)特异性 CAR T 细胞对发光、HER2 表达(FaDu、SCC-47)或 HER2 阴性(MDA-MB-468)CAM 移植肿瘤的疗效。肿瘤移植三天后,将 HER2 特异性 CAR T 细胞应用于生长在 CAM 上的肿瘤。CAR T细胞治疗四天后,用CAR T治疗的HER2表达的FaDu和SCC-47肿瘤显示,根据荧光素酶活性评估,存活的癌细胞减少了。组织学也证实了存活肿瘤细胞的减少,与T细胞处理的对照组相比,CAR T细胞处理的肿瘤中Ki-67染色更低。CD3 染色证实了治疗后 4 天 CAR T 在 CAM 和肿瘤组织中的持续存在。总之,我们的研究结果支持进一步开发小鸡 CAM 作为体内系统,用于快速、可扩展地筛选 CAR T 细胞对人类实体瘤的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chick Embryo Chorioallantoic Membrane as a Platform for Assessing the In Vivo Efficacy of Chimeric Antigen Receptor T-cell Therapy in Solid Tumors.

The fertilized chicken egg chorioallantoic membrane (CAM), a highly vascularized membrane nourishing the developing embryo, also supports rapid growth of three-dimensional vascularized tumors from engrafted cells and tumor explants. Because murine xenograft models suffer limitations of time, cost, and scalability, we propose CAM tumors as a rapid, efficient screening tool for assessing anti-tumor efficacy of chimeric Ag receptor (CAR) T cells against solid tumors. We tested the efficacy of human epidermal growth factor receptor 2 (HER2)-specific CAR T cells against luminescent, HER2-expressing (FaDu, SCC-47) or HER2-negative (MDA-MB-468) CAM-engrafted tumors. Three days after tumor engraftment, HER2-specific CAR T cells were applied to tumors grown on the CAM. Four days post-CAR T cell treatment, HER2-expressing FaDu and SCC-47 tumors treated with CAR T showed reduced viable cancer cells as assessed by luciferase activity. This reduction in viable tumor cells was confirmed by histology, with lower Ki-67 staining observed in CAR T cell-treated tumors relative to T cell-treated controls. Persistence of CAR T in CAM and tumor tissue 4 days post-treatment was confirmed by CD3 staining. Altogether, our findings support further development of the chick CAM as an in vivo system for rapid, scalable screening of CAR T cell efficacy against human solid tumors.

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CiteScore
3.70
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