Heterogeneous Drug Efficacy of an Antibody-Drug Conjugate Visualized Using Simultaneous Imaging of Its Delivery and Intracellular Damage in Living Tumor Tissues
| Autor: | Mayumi Takano-Kasuya, Kohsuke Gonda, Hiroshi Tada, Masayuki Tokunaga, Hideo Higuchi, Narufumi Kitamura, Takanori Ishida, Hiroshi Negishi, Naoko Furusawa, Yasushi Nakano, Yoh Hamada |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Drug Original article Cancer Research Antibody-drug conjugate Chemistry media_common.quotation_subject Cell lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens lcsh:RC254-282 In vitro Microtubule polymerization 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Oncology Microtubule Cell culture 030220 oncology & carcinogenesis medicine Cancer research Intracellular media_common |
| Zdroj: | Translational Oncology, Vol 13, Iss 6, Pp-(2020) Translational Oncology |
| ISSN: | 1936-5233 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|