Journal article
Live Cell Labeling with Terpyridine Derivative Proligands to Measure Cytotoxicity Mediated by Immune Cells
ChemMedChem, Vol.12(23), pp.2006-2013
12/07/2017
DOI: 10.1002/cmdc.201700626
PMCID: PMC5975248
PMID: 29110403
Abstract
Immunotherapy using immune checkpoint inhibitors and CAR-T cells has revolutionized treatment for patients with malignant tumors. However, measuring tumor cell cytotoxicity mediated by immune effector cells in clinical laboratories has been difficult due to the requirement for radioactive substances. In this study, a series of novel terpyridine derivative proligands were synthesized, and a non-radioactive cellular cytotoxicity assay using the newly synthesized compounds was developed for use in preclinical and clinical studies for cancer immunotherapy. Once internalized into target cells, the compounds are hydrolyzed by esterases, resulting in the intracellular accumulation of the negatively charged terpyridine derivatives. When the labeled target cells are recognized and killed by immune effector cells, the integrity of the cell membrane is disrupted, and the terpyridine derivatives are released. Upon combining the culture supernatant with europium (Eu
), the cytotoxicity of immune effector cells for the target cells can be quantitatively determined by measuring the intensity of the Eu
/ligand-derived time-resolved fluorescence. Thus, the assay developed in this study would facilitate the development of novel cancer immunotherapies.
Details
- Title: Subtitle
- Live Cell Labeling with Terpyridine Derivative Proligands to Measure Cytotoxicity Mediated by Immune Cells
- Creators
- Yuki Sakai - Center for Bioinformatics and Molecular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, 852-8523, JapanSatoshi Mizuta - Center for Bioinformatics and Molecular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, 852-8523, JapanAsuka Kumagai - Center for Bioinformatics and Molecular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, 852-8523, JapanMohammed S O Tagod - Center for Bioinformatics and Molecular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, 852-8523, JapanHiroaki Senju - Second Department of Internal Medicine, Nagasaki University Hospital, Nagasaki University, 1-7-1, Sakamoto, Nagsaki, 852-8501, JapanTatsufumi Nakamura - Department of Social Work, Faculty of Human and Social Studies, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki, 859-3298, JapanCraig T Morita - Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, Veterans Affairs Health Care System, 601 Highway 6 West, Research, 151, Iowa City, IA, 52246, USAYoshimasa Tanaka - Center for Bioinformatics and Molecular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, 852-8523, Japan
- Resource Type
- Journal article
- Publication Details
- ChemMedChem, Vol.12(23), pp.2006-2013
- DOI
- 10.1002/cmdc.201700626
- PMID
- 29110403
- PMCID
- PMC5975248
- NLM abbreviation
- ChemMedChem
- ISSN
- 1860-7179
- eISSN
- 1860-7187
- Grant note
- P30 CA086862 / NCI NIH HHS P50 CA097274 / NCI NIH HHS
- Language
- English
- Date published
- 12/07/2017
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094319002771
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