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Screening chemical libraries for modulators of natural killer mediated cytotoxicity

Choi, Paul and Mitchison, Timothy and Clark, John and Huang, Lino (2014) Screening chemical libraries for modulators of natural killer mediated cytotoxicity. Quantitative analysis of resistance to natural killer attacks reveals stepwise killing kinetics.

Abstract

Abstract
Current methods for assaying cell-mediated cytotoxicity have not been demonstrated to function
in cell-based screening assays. However, recent advances in immunotherapy motivate a search
for additional modulators of anti-cancer immune functions. We developed an integrated assay for
screening compound libraries against natural killer (NK) mediated cytotoxicity using a modified
lysis release assay and validation with a granzyme B imaging assays. In an initial screen of
approximately 1000 compounds, we observed and validated new modulators of NK killing
activity with molecular targets previously unassociated with NK signaling pathways. This assay
can be further modified and optimized for discovery of activators and suppressors of anti-cancer
NK activity.
Keywords: natural killer cells, cell-mediated cytotoxicity, biomolecular screening, lysis release
assay, granzyme B

Item Type: Article
Date Deposited: 06 May 2016 23:45
Last Modified: 06 May 2016 23:45
URI: https://oak.novartis.com/id/eprint/22149

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