3 years ago

Global survey of the immunomodulatory potential of common drugs

Global survey of the immunomodulatory potential of common drugs
Nikolaus Krall, Johannes W Bigenzahn, Ulrika Warpman Berglund, Paul Knöbl, Giulio Superti-Furga, Oscar Lopez de la Fuente, Berend Snijder, Thomas Helleday, Monika Sabler, Anna Ringler, Stefan Kubicek, Gregory I Vladimer, Kilian V M Huber, Ulrich Jäger, Charles-Hugues Lardeau, Kumar Sanjiv
Small-molecule drugs may complement antibody-based therapies in an immune-oncology setting, yet systematic methods for the identification and characterization of the immunomodulatory properties of these entities are lacking. We surveyed the immumomodulatory potential of 1,402 small chemical molecules, as defined by their ability to alter the cell-cell interactions among peripheral mononuclear leukocytes ex vivo, using automated microscopy and population-wide single-cell image analysis. Unexpectedly, ~10% of the agents tested affected these cell-cell interactions differentially. The results accurately recapitulated known immunomodulatory drug classes and revealed several clinically approved drugs that unexpectedly harbor the ability to modulate the immune system, which could potentially contribute to their physiological mechanism of action. For instance, the kinase inhibitor crizotinib promoted T cell interactions with monocytes, as well as with cancer cells, through inhibition of the receptor tyrosine kinase MSTR1 and subsequent upregulation of the expression of major histocompatibility complex molecules. The approach offers an attractive platform for the personalized identification and characterization of immunomodulatory therapeutics.

Publisher URL: http://dx.doi.org/10.1038/nchembio.2360

DOI: 10.1038/nchembio.2360

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