An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor Organoids
| العنوان: | An In Vitro System for Evaluating Molecular Targeted Drugs Using Lung Patient-Derived Tumor Organoids |
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| المؤلفون: | Kenju Shimomura, Kazuhito Goda, Nobuhiko Takahashi, Takagi Kosuke, Hirosumi Tamura, Motoki Takagi, Mayu Ogawa, Arisa Higa, Gen Hiyama, Shinya Watanabe, Naoyuki Okabe, Satoshi Muto, Hirotaka Hoshi, Hiroyuki Suzuki |
| المصدر: | Cells Volume 8 Issue 5 Cells, Vol 8, Iss 5, p 481 (2019) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Antibody-drug conjugate, Lung Neoplasms, Cell Survival, Receptor, ErbB-2, medicine.drug_class, molecular targeted therapy, Biopsy, medicine.medical_treatment, immune checkpoint inhibitor, Antineoplastic Agents, Pembrolizumab, Antibodies, Monoclonal, Humanized, Monoclonal antibody, Article, antibody-drug conjugate, Carcinoma, Adenosquamous, Immune system, Cancer immunotherapy, cancer immunity, molecular targeted drugs, medicine, Humans, Epidermal growth factor receptor, lcsh:QH301-705.5, Cells, Cultured, Antibody-dependent cell-mediated cytotoxicity, cancer immunotherapy, 3D cell-analysis system, L-Lactate Dehydrogenase, biology, General Medicine, patient-derived tumor organoid, ErbB Receptors, Organoids, lcsh:Biology (General), Carcinoma, Squamous Cell, Cancer research, biology.protein, Drug Evaluation, antibody drug, Nivolumab, antibody-dependent cellular cytotoxicity |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| DOI: | 10.3390/cells8050481 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3f2f0d7e67de9534633be736c798b618Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3f2f0d7e67de9534633be736c798b618 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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| DOI: | 10.3390/cells8050481 |