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High-Throughput In Vitro Assay using Patient-Derived Tumor Organoids
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High-Throughput In Vitro Assay using Patient-Derived Tumor Organoids

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

Nobuhiko Takahashi1,2, Hirotaka Hoshi3, Arisa Higa4

  • 1Medical-Industrial Translational Research Center, Fukushima Medical University, Fukushima 960-1295, Japan. tkhsnbhk@fmu.ac.jp.

Cells
|May 30, 2019
PubMed

Insights

Patient-derived tumor organoids (PDOs) offer a better preclinical cancer model. These organoids enable in vitro testing of targeted therapies and immunotherapy by mimicking complex tumor and immune cell interactions.

Area of Science:

  • Oncology
  • Preclinical Cancer Models
  • Drug Discovery

Background:

  • Patient-derived tumor organoids (PDOs) offer a more accurate preclinical cancer model than traditional cell cultures.
  • Molecular targeted therapies show efficacy, necessitating in vitro assays for drug potency and immunotherapy evaluation.
  • Complex interactions between tumor cells and immune cells are crucial for immunotherapy assessment.

Purpose of the Study:

  • To establish and validate in vitro assay systems using PDOs for evaluating molecular targeted drugs.
  • To assess the efficacy of various drug classes, including small-molecule inhibitors, monoclonal antibodies, and antibody-drug conjugates.
  • To model immune cell-tumor cell interactions for immunotherapy potential, specifically antibody-dependent cellular cytotoxicity (ADCC) and immune checkpoint inhibitors.

Main Methods:

  • Established PDOs from various human tumors to recapitulate tissue architecture and function.
  • Utilized a high-throughput assay system to evaluate epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) inhibitors.
  • Assessed antibody-dependent cellular cytotoxicity (ADCC) of an anti-HER2 monoclonal antibody and developed evaluation systems for immune checkpoint inhibitors (nivolumab, pembrolizumab) using PDOs.

Main Results:

  • PDOs accurately recapitulated tumor tissue architecture and function.
  • In vitro assay systems demonstrated suitability for evaluating molecular targeted drugs.
  • Effective evaluation of EGFR and HER2 inhibitors, ADCC activity, and immune checkpoint inhibitors was achieved using PDOs.

Conclusions:

  • In vitro assay systems using PDOs are effective for evaluating molecular targeted drugs.
  • PDOs provide a more pathologically relevant model for drug efficacy testing.
  • These PDO-based assays support the development of novel cancer therapies, including targeted agents and immunotherapies.
Keywords:
3D cell-analysis systemantibody drugantibody-dependent cellular cytotoxicityantibody-drug conjugatecancer immunitycancer immunotherapyimmune checkpoint inhibitormolecular targeted drugsmolecular targeted therapypatient-derived tumor organoid

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