An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung 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 PDOs from various human tumors to accurately and efficiently recapitulate the tissue architecture and function. Mol...
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| Format: | Article |
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MDPI AG
2019-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/5/481 |
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| author | Nobuhiko Takahashi Hirotaka Hoshi Arisa Higa Gen Hiyama Hirosumi Tamura Mayu Ogawa Kosuke Takagi Kazuhito Goda Naoyuki Okabe Satoshi Muto Hiroyuki Suzuki Kenju Shimomura Shinya Watanabe Motoki Takagi |
| author_facet | Nobuhiko Takahashi Hirotaka Hoshi Arisa Higa Gen Hiyama Hirosumi Tamura Mayu Ogawa Kosuke Takagi Kazuhito Goda Naoyuki Okabe Satoshi Muto Hiroyuki Suzuki Kenju Shimomura Shinya Watanabe Motoki Takagi |
| author_sort | Nobuhiko Takahashi |
| collection | DOAJ |
| description | Patient-derived tumor organoids (PDOs) represent a promising preclinical cancer model that better replicates disease, compared with traditional cell culture models. We have established PDOs from various human tumors to accurately and efficiently recapitulate the tissue architecture and function. Molecular targeted therapies with remarkable efficacy are currently in use against various tumors. Thus, there is a need for in vitro functional-potency assays that can be used to test the efficacy of molecular targeted drugs and model complex interactions between immune cells and tumor cells to evaluate the potential for cancer immunotherapy. This study represents an in vitro evaluation of different classes of molecular targeted drugs, including small-molecule inhibitors, monoclonal antibodies, and an antibody-drug conjugate, using lung PDOs. We evaluated epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2) inhibitors using a suitable high-throughput assay system. Next, the antibody-dependent cellular cytotoxicity (ADCC) activity of an anti-HER2 monoclonal antibody was evaluated to visualize the interactions of immune cells with PDOs during ADCC responses. Moreover, an evaluation system was developed for the immune checkpoint inhibitors, nivolumab and pembrolizumab, using PDOs. Our results demonstrate that the in vitro assay systems using PDOs were suitable for evaluating molecular targeted drugs under conditions that better reflect pathological conditions. |
| first_indexed | 2024-03-12T06:27:43Z |
| format | Article |
| id | doaj.art-17d67e57786e435daa4a790fdd9cd2c5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T06:27:43Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-17d67e57786e435daa4a790fdd9cd2c52023-09-03T01:47:49ZengMDPI AGCells2073-44092019-05-018548110.3390/cells8050481cells8050481An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor OrganoidsNobuhiko Takahashi0Hirotaka Hoshi1Arisa Higa2Gen Hiyama3Hirosumi Tamura4Mayu Ogawa5Kosuke Takagi6Kazuhito Goda7Naoyuki Okabe8Satoshi Muto9Hiroyuki Suzuki10Kenju Shimomura11Shinya Watanabe12Motoki Takagi13Medical-Industrial Translational Research Center, Fukushima Medical University, Fukushima 960-1295, JapanMedical-Industrial Translational Research Center, Fukushima Medical University, Fukushima 960-1295, JapanMedical-Industrial Translational Research Center, Fukushima Medical University, Fukushima 960-1295, JapanMedical-Industrial Translational Research Center, Fukushima Medical University, Fukushima 960-1295, JapanMedical-Industrial Translational Research Center, Fukushima Medical University, Fukushima 960-1295, JapanResearch and Development, Biological Evaluation Technology 2, Olympus Corporation, Hachioji, Tokyo 192-8512, JapanResearch and Development, SSD Technology Innovation 3, Olympus Corporation, Hachioji, Tokyo 192-8512, JapanResearch and Development, Biological Evaluation Technology 2, Olympus Corporation, Hachioji, Tokyo 192-8512, JapanDepartment of Chest Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Chest Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Chest Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Bioregulation and Pharmacological Medicine, Fukushima Medical University, Fukushima 960-1295, JapanMedical-Industrial Translational Research Center, Fukushima Medical University, Fukushima 960-1295, JapanMedical-Industrial Translational Research Center, Fukushima Medical University, Fukushima 960-1295, JapanPatient-derived tumor organoids (PDOs) represent a promising preclinical cancer model that better replicates disease, compared with traditional cell culture models. We have established PDOs from various human tumors to accurately and efficiently recapitulate the tissue architecture and function. Molecular targeted therapies with remarkable efficacy are currently in use against various tumors. Thus, there is a need for in vitro functional-potency assays that can be used to test the efficacy of molecular targeted drugs and model complex interactions between immune cells and tumor cells to evaluate the potential for cancer immunotherapy. This study represents an in vitro evaluation of different classes of molecular targeted drugs, including small-molecule inhibitors, monoclonal antibodies, and an antibody-drug conjugate, using lung PDOs. We evaluated epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2) inhibitors using a suitable high-throughput assay system. Next, the antibody-dependent cellular cytotoxicity (ADCC) activity of an anti-HER2 monoclonal antibody was evaluated to visualize the interactions of immune cells with PDOs during ADCC responses. Moreover, an evaluation system was developed for the immune checkpoint inhibitors, nivolumab and pembrolizumab, using PDOs. Our results demonstrate that the in vitro assay systems using PDOs were suitable for evaluating molecular targeted drugs under conditions that better reflect pathological conditions.https://www.mdpi.com/2073-4409/8/5/481molecular targeted therapycancer immunotherapycancer immunitymolecular targeted drugsantibody drugantibody-drug conjugateimmune checkpoint inhibitorpatient-derived tumor organoidantibody-dependent cellular cytotoxicity3D cell-analysis system |
| spellingShingle | Nobuhiko Takahashi Hirotaka Hoshi Arisa Higa Gen Hiyama Hirosumi Tamura Mayu Ogawa Kosuke Takagi Kazuhito Goda Naoyuki Okabe Satoshi Muto Hiroyuki Suzuki Kenju Shimomura Shinya Watanabe Motoki Takagi An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor Organoids Cells molecular targeted therapy cancer immunotherapy cancer immunity molecular targeted drugs antibody drug antibody-drug conjugate immune checkpoint inhibitor patient-derived tumor organoid antibody-dependent cellular cytotoxicity 3D cell-analysis system |
| title | An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor Organoids |
| title_full | An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor Organoids |
| title_fullStr | An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor Organoids |
| title_full_unstemmed | An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor Organoids |
| title_short | An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor Organoids |
| title_sort | in vitro system for evaluating molecular targeted drugs using lung patient derived tumor organoids |
| topic | molecular targeted therapy cancer immunotherapy cancer immunity molecular targeted drugs antibody drug antibody-drug conjugate immune checkpoint inhibitor patient-derived tumor organoid antibody-dependent cellular cytotoxicity 3D cell-analysis system |
| url | https://www.mdpi.com/2073-4409/8/5/481 |
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