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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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Autores principales: Takahashi, Nobuhiko, Hoshi, Hirotaka, Higa, Arisa, Hiyama, Gen, Tamura, Hirosumi, Ogawa, Mayu, Takagi, Kosuke, Goda, Kazuhito, Okabe, Naoyuki, Muto, Satoshi, Suzuki, Hiroyuki, Shimomura, Kenju, Watanabe, Shinya, Takagi, Motoki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562414/
https://www.ncbi.nlm.nih.gov/pubmed/31137590
http://dx.doi.org/10.3390/cells8050481
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author Takahashi, Nobuhiko
Hoshi, Hirotaka
Higa, Arisa
Hiyama, Gen
Tamura, Hirosumi
Ogawa, Mayu
Takagi, Kosuke
Goda, Kazuhito
Okabe, Naoyuki
Muto, Satoshi
Suzuki, Hiroyuki
Shimomura, Kenju
Watanabe, Shinya
Takagi, Motoki
author_facet Takahashi, Nobuhiko
Hoshi, Hirotaka
Higa, Arisa
Hiyama, Gen
Tamura, Hirosumi
Ogawa, Mayu
Takagi, Kosuke
Goda, Kazuhito
Okabe, Naoyuki
Muto, Satoshi
Suzuki, Hiroyuki
Shimomura, Kenju
Watanabe, Shinya
Takagi, Motoki
author_sort Takahashi, Nobuhiko
collection PubMed
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.
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spelling pubmed-65624142019-06-17 An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor Organoids Takahashi, Nobuhiko Hoshi, Hirotaka Higa, Arisa Hiyama, Gen Tamura, Hirosumi Ogawa, Mayu Takagi, Kosuke Goda, Kazuhito Okabe, Naoyuki Muto, Satoshi Suzuki, Hiroyuki Shimomura, Kenju Watanabe, Shinya Takagi, Motoki Cells Article 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. MDPI 2019-05-20 /pmc/articles/PMC6562414/ /pubmed/31137590 http://dx.doi.org/10.3390/cells8050481 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Takahashi, Nobuhiko
Hoshi, Hirotaka
Higa, Arisa
Hiyama, Gen
Tamura, Hirosumi
Ogawa, Mayu
Takagi, Kosuke
Goda, Kazuhito
Okabe, Naoyuki
Muto, Satoshi
Suzuki, Hiroyuki
Shimomura, Kenju
Watanabe, Shinya
Takagi, Motoki
An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor Organoids
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562414/
https://www.ncbi.nlm.nih.gov/pubmed/31137590
http://dx.doi.org/10.3390/cells8050481
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