CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
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.
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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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。
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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