Lung Cancer On Chip for Testing Immunotherapy

Han-Jung Liao, Jean-An Chieh, Yu-Chen Chen, Kang-Yun Lee, Y. Chan, S. Ho, Wei-Lun Sun, Yu-Shiuan Wang, Wan-Chen Huang, Wei-Chiao Chang, Cheng-Hsien Liu
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引用次数: 1

Abstract

Immunotherapy is a cancer therapy by enhancing T cell activity. Immune checkpoint, like PD-1/PD-L1, is a key mechanism to regulate T cell activity. The drugs for disrupting the PD-1-PD-L1 interaction are the present promising cancer therapy strategy. Current immunotherapy results in clinical trials show significant improvement in the survival rate in melanoma and lung cancer. However, Due to the high price of immunotherapy reagents, it is challenging to use preclinical experiments to find the appropriate drug dosage. Therefore, here we developed a microfluidic device combined with the following features. The first is highly biocompatible porous photo-initiated cross-linked hydrogel (GelMA) as a 3D culture model to mimic tumor tissue environment. The second is the peripheral channels to stimulate the immune cell environment in blood vessels. The third is the concentration gradient generator to achieve high-throughput multiple drug concentration testing. The results verified that cells could survive in GelMA, and the T cells could infiltrate into GelMA containing cancer cells. Furthermore, this Labchip can simultaneously detect the effects of three doses of drug counterparts on immune cells.
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用于检测免疫治疗的肺癌芯片
免疫疗法是一种通过增强T细胞活性来治疗癌症的疗法。免疫检查点,如PD-1/PD-L1,是调节T细胞活性的关键机制。破坏PD-1-PD-L1相互作用的药物是目前很有前途的癌症治疗策略。目前在临床试验中的免疫治疗结果显示,在黑色素瘤和肺癌的存活率显著提高。然而,由于免疫治疗试剂价格昂贵,通过临床前实验寻找合适的药物剂量是一项挑战。因此,我们开发了一种结合以下特点的微流控装置。第一种是高度生物相容性的多孔光引发交联水凝胶(GelMA)作为模拟肿瘤组织环境的3D培养模型。二是外周通道刺激免疫细胞进入血管环境。三是浓度梯度发生器,实现高通量多药浓度检测。结果证实细胞能够在GelMA中存活,T细胞能够浸润到含有癌细胞的GelMA中。此外,该Labchip可以同时检测三种剂量的药物对应物对免疫细胞的影响。
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