微管阵列膜中空纤维分析（MTAM-HFA）——一种用于癌症免疫治疗（PD-1/PD-L1）的准确快速潜在伴随诊断和药理学研究解决方案。
Microtube Array Membrane Hollow Fiber Assay (MTAM-HFA)-An Accurate and Rapid Potential Companion Diagnostic and Pharmacological Interrogation Solution for Cancer Immunotherapy (PD-1/PD-L1).
机构信息
Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan.
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
出版信息
Biomolecules. 2022 Mar 22;12(4):480. doi: 10.3390/biom12040480.
Immunotherapy is one of the most promising forms of cancer treatment. In particular, immune checkpoint blockers (ICBs) represent some of the leading candidates which many drug developers have heavily invested in. During pre-clinical development and prior to human clinical trials, animal tests are a critical component for determining the safety and efficacy of newly developed ICBs for cancer treatment. In this study, we strive to demonstrate the feasibility of using hollow fiber assay microtube array membrane (MTAM-HFA) in the screening of anti-cancer ICBs. The MTAM-HFA process was carried out by encapsulating peripheral blood mononuclear cells (PBMCs) and the target cancer cells (cell lines or primary cells) and subcutaneously implanting them into Balb/C mice. At predetermined time points combination regimens of PD-1/PD-L1+ were administered accordingly and at a predetermined time point, the MTAMs were retrieved, and cell viability assays were carried out. The outcomes of the MTAM-HFA were compared against the clinical outcome of patients. Clinical comparison demonstrated excellent correlation between the screening outcome of MTAM-HFA of PD-1/PD-L1+ combination therapy and the clinical outcome of the lung cancer patients. Basic cell studies revealed that the utilization of MTAM-HFA in PD-1/PD-L1+ combination therapy revealed enhanced T-cell activity upon the administration of the PD-1/PD-L1 drug; thereby resulting in the reduction of tumor cell viability by up to 70%, and the cytotoxic effects by 82%. The outcome was echoed in the in vivo cell studies. This suggested that the MTAM-HFA system is suitable for use in PD-1/PD-L1+ screening and the accuracy, rapidity and cost effectiveness made it extremely suitable for application as a companion diagnostic system in both personalized medicine for cancer treatment and could potentially be applied to screen for candidate compounds in the development of next generation PD-1/PD-L1+ combination therapies.
免疫疗法是最有前途的癌症治疗形式之一。特别是，免疫检查点抑制剂（ICB）是许多药物开发商大量投资的最主要候选药物之一。在临床前开发和人类临床试验之前，动物试验是确定新开发的 ICB 用于癌症治疗的安全性和有效性的关键组成部分。在这项研究中，我们努力证明使用中空纤维测定微管阵列膜（MTAM-HFA）筛选抗癌 ICB 的可行性。MTAM-HFA 过程通过包裹外周血单核细胞（PBMC）和目标癌细胞（细胞系或原代细胞）并将其皮下植入 Balb/C 小鼠来进行。在预定的时间点给予 PD-1/PD-L1+联合方案，在预定的时间点，取出 MTAMs 并进行细胞活力测定。MTAM-HFA 的结果与患者的临床结果进行了比较。临床比较表明，MTAM-HFA 筛选 PD-1/PD-L1+联合治疗的结果与肺癌患者的临床结果之间存在极好的相关性。基础细胞研究表明，在 PD-1/PD-L1+联合治疗中使用 MTAM-HFA 可增强 T 细胞活性，在给予 PD-1/PD-L1 药物后，肿瘤细胞活力降低了 70%，细胞毒性作用降低了 82%。体内细胞研究结果也证实了这一点。这表明 MTAM-HFA 系统适合用于 PD-1/PD-L1+筛选，其准确性、快速性和成本效益使其非常适合作为癌症治疗个体化医学的伴随诊断系统应用，并且有可能用于筛选下一代 PD-1/PD-L1+联合疗法的候选化合物。
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