A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system.

Autor:	St Pierre C; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America., Guo J; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America., Shin JD; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America., Engstrom LW; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America., Lee HH; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America., Herbert A; Genetics and Pharmacogenomics, Merck Research Laboratories, Boston, MA, United States of America., Surdi L; Drug Metabolism and Pharmacokinetics, Merck Research Laboratories, Boston, MA, United States of America., Baker J; Drug Metabolism and Pharmacokinetics, Merck Research Laboratories, Boston, MA, United States of America., Salmon M; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America., Shah S; Pharmacology, Merck Research Laboratories, Boston, MA, United States of America., Ellis JM; Exploratory Chemistry, Merck Research Laboratories, Boston, MA, United States of America., Houshyar H; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America., Crackower MA; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America., Kleinschek MA; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America., Jones DC; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America., Hicks A; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America., Zaller DM; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America., Alves SE; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America., Ramadas RA; Oncology & Immunology Discovery, Merck Research Laboratories, Boston, MA, United States of America.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2017 Jul 18; Vol. 12 (7), pp. e0180870. Date of Electronic Publication: 2017 Jul 18 (Print Publication: 2017).
DOI:	10.1371/journal.pone.0180870
Abstrakt:	While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the 'immune fingerprint' of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer. Since the mechanistic investigation of pharmacological modulators in a drug discovery setting is largely compound- and mechanism-centric but not comprehensive in terms of immune system impact, we developed a human tissue based functional assay platform to evaluate the impact of pharmacological modulators on a range of innate and adaptive immune functions. Here, we demonstrate that it is possible to generate a qualitative and quantitative immune system impact of pharmacological modulators, which might help better understand and predict the benefit-risk profiles of these compounds in the treatment of immune disorders.
Databáze:	MEDLINE
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