論文

査読有り
2020年6月

Heterogeneous Drug Efficacy of an Antibody-Drug Conjugate Visualized Using Simultaneous Imaging of Its Delivery and Intracellular Damage in Living Tumor Tissues

TRANSLATIONAL ONCOLOGY
  • Kohsuke Gonda
  • ,
  • Hiroshi Negishi
  • ,
  • Mayumi Takano-Kasuya
  • ,
  • Narufumi Kitamura
  • ,
  • Naoko Furusawa
  • ,
  • Yasushi Nakano
  • ,
  • Yoh Hamada
  • ,
  • Masayuki Tokunaga
  • ,
  • Hideo Higuchi
  • ,
  • Hiroshi Tada
  • ,
  • Takanori Ishida

13
6
開始ページ
100764
終了ページ
100764
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.tranon.2020.100764
出版者・発行元
ELSEVIER SCIENCE INC

Anticancer drug efficacy varies because the delivery of drugs within tumors and tumor responses are heterogeneous; however, these features are often more homogenous in vitro. This difference makes it difficult to accurately determine drug efficacy. Therefore, it is important to use living tumor tissues in preclinical trials to observe the heterogeneity in drug distribution and cell characteristics in tumors. In the present study, to accurately evaluate the efficacy of an antibody-drug conjugate (ADC) containing a microtubule inhibitor, we established a cell line that expresses a fusion of end-binding protein 1 and enhanced green fluorescent protein that serves as a microtubule plus-end-tracking protein allowing the visualization of microtubule dynamics. This cell line was xenografted into mice to create a model of living tumor tissue. The tumor cells possessed a greater number of microtubules with plus-ends, a greater number of meandering microtubules, and a slower rate of microtubule polymerization than the in vitro cells. In tumor tissues treated with fluorescent dye-labeled ADCs, heterogeneity was observed in the delivery of the drug to tumor cells, and microtubule dynamics were inhibited in a concentration-dependent manner. Moreover, a difference in drug sensitivity was observed between in vitro cells and tumor cells; compared with in vitro cells, tumor cells were more sensitive to changes in the concentration of the ADC. This study is the first to simultaneously evaluate the delivery and intracellular efficacy of ADCs in living tumor tissue. Accurate evaluation of the efficacy of ADCs is important for the development of effective anticancer drugs.


リンク情報
DOI
https://doi.org/10.1016/j.tranon.2020.100764
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000537451300006&DestApp=WOS_CPL

エクスポート
BibTeX RIS