比较 PD-L1 阻断抗体的小鼠胰腺类器官模型。
A mouse pancreatic organoid model to compare PD-L1 blocking antibodies.
机构信息
Division of Biotechnology Review and Research 1, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Oncology Center of Excellence, US Food and Drug Administration, Silver Spring, Maryland, USA.
出版信息
MAbs. 2022 Jan-Dec;14(1):2139886. doi: 10.1080/19420862.2022.2139886.
Immune checkpoint inhibitors (ICIs) have changed the therapeutic landscape for cancer patients, but diabetes, a rare, severe immune-related endocrinopathy, is linked to ICI therapy. It is unclear whether glycosylation of ICIs may play a role in the development of this adverse event and how the physiological effects of different ICIs on pancreatic cells should be evaluated. We used a mouse pancreatic organoid model to compare three PD-L1 blocking antibodies in the presence or absence of IFNγ using a metabolic bioanalyzer. Modulation of ICI glycosylation altered its metabolic effects on mouse pancreatic organoids, suggesting that this model could be used to monitor and compare ICIs and to study the mechanisms underlying the development of IC-mediated diabetes.
免疫检查点抑制剂（ICIs）改变了癌症患者的治疗格局，但糖尿病是一种罕见的严重免疫相关内分泌疾病，与 ICI 治疗有关。目前尚不清楚 ICI 的糖基化是否可能在这一不良事件的发展中发挥作用，以及应如何评估不同 ICI 对胰腺细胞的生理影响。我们使用小鼠胰腺类器官模型，在存在或不存在 IFNγ的情况下，使用代谢生物分析仪比较了三种 PD-L1 阻断抗体。ICI 糖基化的调节改变了其对小鼠胰腺类器官的代谢影响，表明该模型可用于监测和比较 ICI，并研究 IC 介导的糖尿病发展的机制。
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