Walter Yohan, Hubbard Anne, Benoit Allie, Jank Erika, Salas Olivia, Jordan Destiny, Ekpenyong Andrew
Department of Physics, Creighton University, Omaha, NE 68178, USA.
Department of Biology, Creighton University, Omaha, NE 68178, USA.
Biomedicines. 2022 Jul 26;10(8):1796. doi: 10.3390/biomedicines10081796.
Glioblastoma (GBM) is the most common primary brain tumor. Due to high resistance to treatment, local invasion, and a high risk of recurrence, GBM patient prognoses are often dismal, with median survival around 15 months. The current standard of care is threefold: surgery, radiation therapy, and chemotherapy with temozolomide (TMZ). However, patient survival has only marginally improved. Radioimmunotherapy (RIT) is a fourth modality under clinical trials and aims at combining immunotherapeutic agents with radiotherapy. Here, we develop in vitro assays for the rapid evaluation of RIT strategies. Using a standard cell irradiator and an Electric Cell Impedance Sensor, we quantify cell migration following the combination of radiotherapy and chemotherapy with TMZ and RIT with durvalumab, a PD-L1 immune checkpoint inhibitor. We measure cell survival using a cloud-based clonogenic assay. Irradiated T98G and U87 GBM cells migrate significantly (p < 0.05) more than untreated cells in the first 20−40 h post-treatment. Addition of TMZ increases migration rates for T98G at 20 Gy (p < 0.01). Neither TMZ nor durvalumab significantly change cell survival in 21 days post-treatment. Interestingly, durvalumab abolishes the enhanced migration effect, indicating possible potency against local invasion. These results provide parameters for the rapid supplementary evaluation of RIT against brain tumors.
胶质母细胞瘤（GBM）是最常见的原发性脑肿瘤。由于对治疗的高抗性、局部侵袭以及高复发风险，GBM患者的预后通常很差，中位生存期约为15个月。当前的标准治疗方案包括三个方面：手术、放射治疗以及使用替莫唑胺（TMZ）进行化疗。然而，患者的生存期仅略有改善。放射免疫疗法（RIT）是一种正在进行临床试验的第四种治疗方式，旨在将免疫治疗药物与放射治疗相结合。在此，我们开发了体外试验以快速评估RIT策略。使用标准细胞辐照器和电细胞阻抗传感器，我们量化了放射治疗与TMZ化疗以及RIT与程序性死亡受体配体1（PD-L1）免疫检查点抑制剂度伐利尤单抗联合使用后的细胞迁移情况。我们使用基于云的克隆形成试验来测量细胞存活率。在治疗后的最初20 - 40小时内，接受辐照的T98G和U87 GBM细胞的迁移明显（p < 0.05）多于未处理的细胞。添加TMZ可提高20 Gy剂量下T98G细胞的迁移率（p < 0.01）。TMZ和度伐利尤单抗在治疗后21天均未显著改变细胞存活率。有趣的是，度伐利尤单抗消除了增强的迁移效应，表明其可能对局部侵袭具有抑制作用。这些结果为快速补充评估针对脑肿瘤的RIT提供了参数。
