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

Autor:	Gonda K; Department of Medical Physics, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8575, Japan. Electronic address: gonda@med.tohoku.ac.jp., Negishi H; Bio Systems Development Group, Bio Advanced Technology Division, Corporate R&D Headquarters, KONICAMINOLTA. INC., Hino, Tokyo, 191-8511, Japan., Takano-Kasuya M; Department of Medical Physics, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8575, Japan., Kitamura N; Department of Medical Physics, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8575, Japan., Furusawa N; Bio Systems Development Group, Bio Advanced Technology Division, Corporate R&D Headquarters, KONICAMINOLTA. INC., Hino, Tokyo, 191-8511, Japan., Nakano Y; Bio Systems Development Group, Bio Advanced Technology Division, Corporate R&D Headquarters, KONICAMINOLTA. INC., Hino, Tokyo, 191-8511, Japan., Hamada Y; Department of Gastroenterological Surgery, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8574, Japan., Tokunaga M; Department of Medical Physics, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8575, Japan., Higuchi H; Department of Physics, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan., Tada H; Department of Breast and Endocrine Surgical Oncology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8574, Japan., Ishida T; Department of Breast and Endocrine Surgical Oncology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8574, Japan.
Jazyk:	angličtina
Zdroj:	Translational oncology [Transl Oncol] 2020 Jun; Vol. 13 (6), pp. 100764. Date of Electronic Publication: 2020 May 11.
DOI:	10.1016/j.tranon.2020.100764
Abstrakt:	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. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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