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Global survey of the immunomodulatory potential of common drugs.

ABSTRACT: 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.

SUBMITTER: Vladimer GI

PROVIDER: S-EPMC5438060 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Global survey of the immunomodulatory potential of common drugs.

Vladimer Gregory I GI Snijder Berend B Krall Nikolaus N Bigenzahn Johannes W JW Huber Kilian V M KVM Lardeau Charles-Hugues CH Sanjiv Kumar K Ringler Anna A Berglund Ulrika Warpman UW Sabler Monika M de la Fuente Oscar Lopez OL Knöbl Paul P Kubicek Stefan S Helleday Thomas T Jäger Ulrich U Superti-Furga Giulio G

Nature chemical biology 20170424 6

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. Unexpecte ...[more]

PMID: 28437395

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Project description:BACKGROUND:Immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide; IMID) are widely used in the treatment of multiple myeloma patients. To date, few data are available on IMID adherence in multiple myeloma patients. The aim of our study was to evaluate IMID adherence and to compare two indirect methods to measure IMID adherence in multiple myeloma patients: a specific questionnaire and the medication possession ratio (MPR). Another aim was to explore this specific questionnaire for the assessment of IMID adherence in multiple myeloma patients. METHODS:All consecutive multiple myeloma patients, with at least two consecutive dispensations of thalidomide, lenalidomide or pomalidomide in our hospital were included in this prospective study. IMID adherence was measured using a specific questionnaire and the medication possession ratio. Relationship between the questionnaire scores and variables of interest was evaluated by multiple linear regression with a robust variance estimator. FINDINGS:Sixty-three patients were included in our study. The mean questionnaire score was 8.2±1.2 and the mean medication possession ratio value was 0.97±0.06. A total of 76% of patients were considered adherent according to the questionnaire (i.e. score ≥ 8), 94% according to the medication possession ratio (i.e. MPR ≥ 0.90), and 70% according to the questionnaire and the medication possession ratio. No statistically significant linear association was observed between the questionnaire score and any variables of interest including medication possession ratio. All Cronbach's alpha were relatively low (range 0.0342-0.2443), showing a low correlation of the different questions with the questionnaire score. CONCLUSIONS:Our study is the first prospective study evaluating IMID adherence in multiple myeloma patients in real life. The high adherence to IMIDs reported here, regardless of the drug, is encouraging considering the efficacy, toxicity and elevated cost of IMIDs. The specific questionnaire should be used with caution to evaluate IMID adherence.

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Global survey of the immunomodulatory potential of common drugs.

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Global survey of the immunomodulatory potential of common drugs.

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