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鸡胚绒毛尿囊膜作为评估实体瘤中 CAR-T 细胞治疗体内疗效的平台

英文原题:Chick Embryo Chorioallantoic Membrane as a Platform for Assessing the In Vivo Efficacy of Chimeric Antigen Receptor T-cell Therapy in Solid Tumors.

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Chick Embryo Chorioallantoic Membrane as a Platform for Assessing the In Vivo Efficacy of Chimeric Antigen Receptor T-cell Therapy in Solid Tumors.

PubMed 2024/08/01(内容时间) Immunohorizons

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中文摘要

受精的鸡胚绒毛尿囊膜(CAM)是一种高度血管化的膜,为发育中的胚胎提供营养,同时也支持植入的细胞和肿瘤外植体快速生长为三维血管化肿瘤。由于小鼠异种移植模型存在时间、成本和可扩展性方面的局限,我们提出将 CAM 肿瘤作为一种快速、高效的筛选工具,用于评估嵌合抗原受体(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 细胞对表达荧光素酶的 HER2 阳性(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 CAM 上生长的肿瘤。CAR-T 细胞治疗后四天,通过荧光素酶活性评估显示,经 CAR-T 治疗的 HER2 表达阳性 FaDu 和 SCC-47 肿瘤中存活癌细胞减少。这种存活肿瘤细胞的减少经组织学证实,与 T 细胞治疗的对照组相比,CAR-T 细胞治疗的肿瘤中 Ki-67 染色更低。治疗后四天,通过 CD3 染色证实了 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鸡胚 CAM 作为一种体内系统,用于快速、可扩展地筛选 CAR-T 细胞对人实体瘤的疗效。

展开英文摘要原文

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.

论文信息

作者
Nipper AJ、Warren EAK、Liao KS、Liu HC、Michikawa C、Porter CE、Wells GA、Villanueva M
单位
Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston, TX.United States
文献类型
美国 NIH 资助研究 · 非美国政府资助研究
期刊
ImmunoHorizons2024 Aug 1
原文标识
PubMed 39225630 · DOI 10.4049/immunohorizons.2400059