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Updated: Jan 29, 2026

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三维瘤球体揭示了B7-H3 CAR T细胞透动力学和微环境诱导的功能重编程在固体瘤中

Feng Chen^1,2, Ke Ning¹, Yuanyuan Xie¹

¹Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, School of Materials and Energy, Southwest University, Chongqing 400715, China.

|January 28, 2026

概括

这项研究引入了一种3D瘤球形模型,以克服评估化学抗原受体 (CAR) T细胞治疗固体瘤的局限性. 该平台有效地建模瘤微环境 (TME),并评估CAR T细胞对癌症球体的疗效.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物技术是生物技术.

背景情况:

化学抗原受体 (CAR) T细胞疗法在血液癌症中表现有前途,但由于瘤微环境 (TME),在固体瘤中面临挑战.
现有的二维细胞培养模型无法准确地表示复杂的TME,限制了对CAR T细胞治疗在固体瘤中的疗效的评估.

研究的目的:

验证3D瘤球形平台,用于评估固体瘤中CAR T细胞治疗.
评估TME对CAR T细胞功能和疗效的影响,使用一种新的3D模型.

主要方法:

开发了一个3D瘤球形模型,使用糖微波系统从固体瘤细胞系产生均的B7-H3-阳性球形.
在3D球形中通过流细胞计分析了TME相关的免疫调制 (B7-H3,MHC I/II,APM).
与B7-H3 CAR T细胞共同培养的球体来评估细胞毒性,瘤活力以及CAR T细胞激活,耗尽和细胞因子的产生.

主要成果:

3D平台成功地从前列腺癌 (DU 145) 和乳腺癌 (SUM159) 细胞系生成了B7-H3阳性球体.
3D球体表现出类似TME的免疫逃避特征,降低MHC-I和抗原处理机器 (APM) 的调节,同时提高MHC-II和calreticulin.
卡尔-T细胞有效地透到球体中,表现出细胞毒性,结构性破坏,以及增强的激活,耗尽和效应器功能,包括增加IFN-γ和TNF-α的产生.

结论:

经过验证的3D瘤球形平台有效地回顾了与CAR T细胞治疗相关的关键TME约束.
这种3D模型提供了一种可行且具有成本效益的临床前工具,用于评估固体瘤中CAR T细胞疗法,其性能优于传统的2D分析.

关键词:

三维瘤球形体 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 B7-H3 在CAR T细胞中,透T细胞的透情况免疫疗法免疫疗法瘤微环境是一个微环境.

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