肿瘤细胞治疗研究
英文原题：A tumor-on-a-chip for in vitro study of CAR-T cell immunotherapy in solid tumors.
我们对肿瘤-免疫相互作用的有限认识，仍是推进嵌合抗原受体（CAR）-T 细胞疗法治疗实体恶性肿瘤的关键障碍。
我们对癌症与免疫系统相互作用的认识仍然有限，这是推进嵌合抗原受体（CAR）T细胞疗法治疗实体瘤的一项关键障碍。本文介绍一种微工程化系统，可使人肿瘤组织外植体形成血管网络，并对免疫细胞进行可控灌流，从而模拟肿瘤微环境中的CAR-T细胞活性。研究者首先利用具有血管网络的人肺腺癌肿瘤，展示了肿瘤芯片系统模拟、可视化和探究CAR-T细胞功能的能力。随后，在恶性胸膜间皮瘤模型中测试了一种趋化因子引导的CAR-T细胞工程策略，并在相应的体内小鼠模型中验证结果。最后，研究提出一种可通过药物调节、以提高CAR-T细胞治疗肺腺癌疗效的潜在靶点，并报告了通过全局代谢组学分析发现的相关生物标志物。这一微生理系统为推进癌症及其他疾病的过继细胞疗法开发，提供了有前景的体外技术。
Our limited understanding of cancer-immune interactions remains a critical barrier to advancing chimeric antigen receptor (CAR)-T cell therapy for solid malignancies. Here, we present a microengineered system that enables vascularization of human tumor explants and their controlled perfusion with immune cells to model the activity of CAR-T cells in the tumor microenvironment. Using vascularized human lung adenocarcinoma tumors, we first demonstrate the ability of our tumor-on-a-chip system to simulate, visualize and interrogate CAR-T cell function. We then test a chemokine-directed CAR-T cell engineering strategy in a model of malignant pleural mesothelioma and validate our findings in a matching in vivo mouse model. Finally, we describe a potential therapeutic target that can be pharmacologically modulated to increase the efficacy of CAR-T cells in lung adenocarcinoma, for which we present biomarkers identified by global metabolomics analysis. Our microphysiological system provides promising in vitro technology to advance the development of adoptive cell therapies for cancer and other diseases.
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