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Live Cell Labeling with Terpyridine Derivative Proligands to Measure Cytotoxicity Mediated by Immune Cells


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Title: Live Cell Labeling with Terpyridine Derivative Proligands to Measure Cytotoxicity Mediated by Immune Cells
Authors: Sakai, Yuki / Mizuta, Satoshi / Kumagai, Asuka / Tagod, Mohammed S. O. / Senju, Hiroaki / Nakamura, Tatsufumi / Morita, Craig T. / Tanaka, Yoshimasa
Issue Date: 7-Dec-2017
Publisher: Wiley-VCH Verlag GmbH & Co.
Citation: ChemMedChem, 12(23), pp.2006-2013; 2017
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 (Eu3+), the cytotoxicity of immune effector cells for the target cells can be quantitatively determined by measuring the intensity of the Eu3+/ligand-derived time-resolved fluorescence. Thus, the assay developed in this study would facilitate the development of novel cancer immunotherapies.
Keywords: cancer immunotherapy / cytotoxicity assays / NK cells / T cells / terpyridine proligands
URI: http://hdl.handle.net/10069/38318
ISSN: 18607179
DOI: 10.1002/cmdc.201700626
Rights: © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim / This is the peer reviewed version of the following article: ChemMedChemVolume, 12(23), pp.2006-2013; 2017, which has been published in final form at http://dx.doi.org/10.1002/cmdc.201700626. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/38318

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