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Open AccessFeature PaperEditor’s ChoiceArticle

An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor Organoids

1
Medical-Industrial Translational Research Center, Fukushima Medical University, Fukushima 960-1295, Japan
2
Department of Bioregulation and Pharmacological Medicine, Fukushima Medical University, Fukushima 960-1295, Japan
3
Research and Development, Biological Evaluation Technology 2, Olympus Corporation, Hachioji, Tokyo 192-8512, Japan
4
Research and Development, SSD Technology Innovation 3, Olympus Corporation, Hachioji, Tokyo 192-8512, Japan
5
Department of Chest Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan
*
Author to whom correspondence should be addressed.
Cells 2019, 8(5), 481; https://doi.org/10.3390/cells8050481
Received: 25 April 2019 / Revised: 14 May 2019 / Accepted: 18 May 2019 / Published: 20 May 2019
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. View Full-Text
Keywords: 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 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
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Takahashi, N.; Hoshi, H.; Higa, A.; Hiyama, G.; Tamura, H.; Ogawa, M.; Takagi, K.; Goda, K.; Okabe, N.; Muto, S.; Suzuki, H.; Shimomura, K.; Watanabe, S.; Takagi, M. An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor Organoids. Cells 2019, 8, 481.

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