PO.CH01.02 · 化学

一个用于高通量筛选和药物发现的稳健的类器官平台

A robust organoid-based platform for high-throughput screening and drug discovery

编号 6404 展板 4 时间 4/21 02:00–05:00 区域 Section 39 主讲 Sylvia Boj, PhD
分会场 Screening and Technology Advances for Probe and Drug Discovery
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作者与单位 Authors & Affiliations

Rene Overmeer, Mariana Martins Costa Silva, Gerben ten Hag, Mayke Doorn, Yasmine Abouleila, Ricardo Korporaal, Francisco Morales Rodriguez, Merel Derksen, Carla Verissimo, Robert G. J. Vries, Sylvia F. Boj

HUB Organoids B.V., Utrecht, Netherlands

摘要 Abstract

中文摘要
患者来源类器官(PDO),即HUB Organoids®,是由正常和恶性上皮组织的成体干细胞生成的先进3D模型,并储存在高质量的生物样本库中以确保可重复性。HUB Organoids忠实地再现了原始组织的生理学、分子异质性以及形态学和功能特征,有效地模拟患者反应,弥合了实验室研究与临床应用之间的差距——将"患者带入实验室"。Petosemtamab(MCLA-158)的快速开发例证了类器官技术在药物开发中的价值,因为使用传统的2D模型无法识别该靶标。进一步支持这一点的是,近期发表的论文突显了类器官预测转移性结直肠癌治疗反应的能力。在此,我们展示了中至高通量筛选的能力,可并行评估跨多个类器官模型的6,000多种化合物。可用的读出方式包括基于酶标仪的活力检测(CellTiter-Glo 3D)和基于成像的检测(CyQuant)。除了初步的大规模筛选外,我们平台的精确性和可重复性还促进了后续构效关系(SAR)研究的快速迭代或跨多种患者模型的扩展筛选。总之,我们提供了一个稳健、临床相关且经济高效的平台,以支持从早期化合物筛选到高级验证研究的药物开发。
查看英文原文 English abstract
Patient-derived organoids (PDOs), or HUB Organoids®, are advanced 3D models generated from adult stem cells of normal and malignant epithelial tissues and stored in high-quality biobanks to ensure reproducibility. HUB Organoids faithfully recapitulate the physiology, molecular heterogeneity, and morphological and functional characteristics of the original tissue, effectively mimicking patient response and bridging the gap between laboratory research and clinical application-bringing the “patient into the lab.” The rapid development of Petosemtamab (MCLA-158) exemplifies the value of organoid technology in drug development, as this target could not have been identified using conventional 2D models. Further supporting this, recent publications highlight the ability of organoids to predict treatment response in metastatic colorectal cancer. Here, we present our capabilities for medium- to high-throughput screening, enabling the evaluation of over 6,000 compounds across multiple organoid models in parallel. Available readouts include plate reader-based viability assays (CellTiter-Glo 3D) and imaging-based assays (CyQuant). Beyond initial large-scale screening, rapid iterations of follow-up structure-activity relationship (SAR) studies or expanded screening across diverse patient models are facilitated by the precision and reproducibility of our platform. In summary, we offer a robust, clinically relevant, and cost-effective platform to support drug development from early-stage compound screening to advanced validation studies.
利益披露 Disclosure
R. Overmeer, None.. M. M. Costa Silva, None.. G. ten Hag, None.. M. Doorn, None.. Y. Abouleila, None.. R. Korporaal, None.. F. Morales Rodriguez, None.. M. Derksen, None.. C. Verissimo, None.. R. G. J. Vries, None.. S. F. Boj, None.

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