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An In Vitro System for Evaluating Anticancer Drugs Using Patient-Derived Tumor Organoids

Patient-derived tumor organoids (PDOs) represent a promising preclinical cancer model that better replicates disease, compared with traditional cell culture models. We have established a novel series of patient-derived tumor organoids (PDOs) from various types of tumor tissues from the Fukushima Translational Research Project, which are designated as Fukushima (F)-PDOs. F-PDOs could be cultured for >6 months and formed cell clusters with similar morphologies to their source tumors. Comparative histological and comprehensive gene-expression analyses also demonstrated that the characteristics of PDOs were similar to those of their source tumors, even following long-term expansion in culture. In addition, suitable high-throughput assay systems were constructed for each F-PDO in 96- and 384-well plate formats.

This presentation represents the characteristics of F-PDOs and an in vitro evaluation of different classes of anticancer drugs, including chemotherapeutic, molecular targeted, antibody and immunotherapeutic drugs, using F-PDOs. We firstly evaluated chemotherapeutic drugs such as paclitaxel and carboplatinand, and molecular targeted drugs such as epidermal growth factor receptor (EGFR) inhibitors using a suitable high-throughput assay system. In addition, an evaluation system for the antibody-dependent cellular cytotoxic activity of anti-EGFR antibody and the cytotoxic activity of activated lymphocytes, such as cytotoxic T lymphocytes and natural killer cells, was constructed. Moreover, an evaluation system was developed for the immune checkpoint inhibitors, nivolumab and pembrolizumab, using F-PDOs. Our results demonstrate that the in vitro assay systems using F-PDOs were suitable for evaluating different classes of anticancer drugs under conditions that better reflect pathological conditions. In addition, our results indicated that F-PDOs have structural characteristics enabling the construction of an evaluation system for anticancer drugs, based on structural changes of F-PDO found with a 3D cell-analysis system, demonstrating that 3D cell analysis is a powerful tool for analyzing the characteristics of PDOs.

An In Vitro System for Evaluating Anticancer Drugs Using Patient-Derived Tumor Organoids

Patient-derived tumor organoids (PDOs) represent a promising preclinical cancer model that better replicates disease, compared with traditional cell culture models. We have established a novel series of patient-derived tumor organoids (PDOs) from various types of tumor tissues from the Fukushima Translational Research Project, which are designated as Fukushima (F)-PDOs. F-PDOs could be cultured for >6 months and formed cell clusters with similar morphologies to their source tumors. Comparative histological and comprehensive gene-expression analyses also demonstrated that the characteristics of PDOs were similar to those of their source tumors, even following long-term expansion in culture. In addition, suitable high-throughput assay systems were constructed for each F-PDO in 96- and 384-well plate formats.

This presentation represents the characteristics of F-PDOs and an in vitro evaluation of different classes of anticancer drugs, including chemotherapeutic, molecular targeted, antibody and immunotherapeutic drugs, using F-PDOs. We firstly evaluated chemotherapeutic drugs such as paclitaxel and carboplatinand, and molecular targeted drugs such as epidermal growth factor receptor (EGFR) inhibitors using a suitable high-throughput assay system. In addition, an evaluation system for the antibody-dependent cellular cytotoxic activity of anti-EGFR antibody and the cytotoxic activity of activated lymphocytes, such as cytotoxic T lymphocytes and natural killer cells, was constructed. Moreover, an evaluation system was developed for the immune checkpoint inhibitors, nivolumab and pembrolizumab, using F-PDOs. Our results demonstrate that the in vitro assay systems using F-PDOs were suitable for evaluating different classes of anticancer drugs under conditions that better reflect pathological conditions. In addition, our results indicated that F-PDOs have structural characteristics enabling the construction of an evaluation system for anticancer drugs, based on structural changes of F-PDO found with a 3D cell-analysis system, demonstrating that 3D cell analysis is a powerful tool for analyzing the characteristics of PDOs.

Experts
Dr. Motoki Takagi
Professor
Medical-Industrial Translational Research Center, Fukushima Medical University

Dr. Motoki Takagi received PhD from Graduate School of Agriculture and Life Sciences, the University of Tokyo in 2001. Then he continued his research as a postdoctoral fellow at Institute of Molecular and Cellular Biosciences, the University of Tokyo. He was engaged in the research of nucleic acid drugs at Genencare Research Institute, Co. Ltd. since 2002. Since 2006, he conducted drug discovery research at Biological Systems Control Team, Biomedicinal Information Research Center, Japan Biological Informatics Consortium. Since 2012, he has been researching chemical biology as an associate professor at Fukushima Medical University and became a professor in 2014.

An In Vitro System for Evaluating Anticancer Drugs Using Patient-Derived Tumor OrganoidsMar 29 2024
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