决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:A spatially resolved implantable microdevice for multiplexed in situ screening of engineered cellular therapies in solid tumors.
实体瘤细胞免疫疗法的临床转化仍然受限,原因是缺乏足够的工具来评估原生肿瘤微环境中的治疗功能。
实体瘤细胞免疫疗法的临床转化仍受限于缺乏足够的工具来评估原生肿瘤微环境中的治疗功能。在此,我们展示了一种微型可植入微装置(IMD),能够在活体肿瘤内直接对多种T细胞疗法的递送和筛选进行空间分辨和多路复用。这种可定制的IMD由离散的纤维蛋白填充储库组成,可独立装载不同的免疫细胞制剂,从而在同一肿瘤块内实现空间受限的释放和区域特异性的免疫-肿瘤相互作用。在胶质母细胞瘤异种移植模型中使用该平台,我们同时递送了靶向EGFR的CAR-T细胞和对照T细胞,并通过基于IHC的定量图像分析和多重免疫荧光分析了邻近组织。与CAR-T细胞储库相邻的储库周围区域表现出密集的CD8+浸润、cleaved caspase-3介导的细胞凋亡以及Ki67表达抑制,而对照区域则活性极低。我们相信我们的IMD平台有助于多种免疫细胞疗法的平行体内评估,为加速成功开发个性化过继细胞疗法提供了一种转化工具。
The clinical translation of cellular immunotherapies for solid tumors remains limited by the lack of adequate tools to evaluate therapeutic function within the native tumor microenvironment. Here, we demonstrate a miniaturized implantable microdevice (IMD) capable of spatially resolving and multiplexing the delivery and screening of multiple T cell therapies directly within live tumors. This customizable IMD is comprised of discrete fibrin-filled reservoirs that can be independently loaded with distinct immune cell formulations, which enables spatially confined release and region-specific immune-tumor interactions within the same tumor mass. Using this platform in glioblastoma xenografts, we simultaneously delivered EGFR-targeting CAR-T cells and control T cells and analyzed adjacent tissues via IHC-based quantitative image analysis and multiplexed immunofluorescence. The perireservoir region adjacent to CAR-T cell reservoirs exhibited dense CD8 + infiltration, cleaved caspase-3-mediated apoptosis, and suppressed Ki67 expression, in contrast to minimal activity in control regions. We believe our IMD platform facilitates the parallel in vivo evaluation of multiple immune cell therapies, providing a translational tool to accelerate the development of successful personalized adoptive cell therapies.
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