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

Autor: J. Michael Ellis, Ravisankar A. Ramadas, Hyun-Hee Lee, Laura Surdi, Hani Houshyar, Cristina St. Pierre, Melanie A. Kleinschek, Alan Herbert, John H. Shin, Stephen E. Alves, Dallas C. Jones, James Baker, Michael A. Crackower, Jane Guo, Alexandra Hicks, Sanjiv J. Shah, Laura Engstrom, Dennis M. Zaller, Michael Salmon
Rok vydání: 2017
Předmět:
0301 basic medicine
Chemokine
Neutrophils
T-Lymphocytes
medicine.medical_treatment
Drug Evaluation
Preclinical
Gene Expression
lcsh:Medicine
NK cells
Disease
Bioinformatics
White Blood Cells
Animal Cells
Medicine and Health Sciences
lcsh:Science
Immune Response
media_common
Phagocytes
Multidisciplinary
biology
T Cells
Organic Compounds
Drug discovery
Toll-Like Receptors
Immunosuppression
Killer Cells
Natural
Chemistry
Physical Sciences
Cellular Types
Chemokines
Research Article
Biotechnology
Drug
Immune Cells
media_common.quotation_subject
Immunology
Cytotoxic T cells
Small Molecule Libraries
03 medical and health sciences
Immune system
Genetics
medicine
Humans
Adverse effect
Blood Cells
business.industry
Organic Chemistry
lcsh:R
Chemical Compounds
Biology and Life Sciences
Cancer
Cell Biology
biochemical phenomena
metabolism
and nutrition
medicine.disease
030104 developmental biology
Small Molecules
Immune System
Leukocytes
Mononuclear
biology.protein
bacteria
lcsh:Q
Reactive Oxygen Species
Transcriptome
business
Zdroj: PLoS ONE, Vol 12, Iss 7, p e0180870 (2017)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0180870
Popis: 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: OpenAIRE
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