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QSP‐IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno‐Oncology Applications

Immunotherapy has shown great potential in the treatment of cancer; however, only a fraction of patients respond to treatment, and many experience autoimmune‐related side effects. The pharmaceutical industry has relied on mathematical models to study the behavior of candidate drugs and more recently...

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Detalles Bibliográficos
Autores principales: Sové, Richard J., Jafarnejad, Mohammad, Zhao, Chen, Wang, Hanwen, Ma, Huilin, Popel, Aleksander S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499194/
https://www.ncbi.nlm.nih.gov/pubmed/32618119
http://dx.doi.org/10.1002/psp4.12546
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author Sové, Richard J.
Jafarnejad, Mohammad
Zhao, Chen
Wang, Hanwen
Ma, Huilin
Popel, Aleksander S.
author_facet Sové, Richard J.
Jafarnejad, Mohammad
Zhao, Chen
Wang, Hanwen
Ma, Huilin
Popel, Aleksander S.
author_sort Sové, Richard J.
collection PubMed
description Immunotherapy has shown great potential in the treatment of cancer; however, only a fraction of patients respond to treatment, and many experience autoimmune‐related side effects. The pharmaceutical industry has relied on mathematical models to study the behavior of candidate drugs and more recently, complex, whole‐body, quantitative systems pharmacology (QSP) models have become increasingly popular for discovery and development. QSP modeling has the potential to discover novel predictive biomarkers as well as test the efficacy of treatment plans and combination therapies through virtual clinical trials. In this work, we present a QSP modeling platform for immuno‐oncology (IO) that incorporates detailed mechanisms for important immune interactions. This modular platform allows for the construction of QSP models of IO with varying degrees of complexity based on the research questions. Finally, we demonstrate the use of the platform through two example applications of immune checkpoint therapy.
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spelling pubmed-74991942020-09-25 QSP‐IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno‐Oncology Applications Sové, Richard J. Jafarnejad, Mohammad Zhao, Chen Wang, Hanwen Ma, Huilin Popel, Aleksander S. CPT Pharmacometrics Syst Pharmacol Tutorial Immunotherapy has shown great potential in the treatment of cancer; however, only a fraction of patients respond to treatment, and many experience autoimmune‐related side effects. The pharmaceutical industry has relied on mathematical models to study the behavior of candidate drugs and more recently, complex, whole‐body, quantitative systems pharmacology (QSP) models have become increasingly popular for discovery and development. QSP modeling has the potential to discover novel predictive biomarkers as well as test the efficacy of treatment plans and combination therapies through virtual clinical trials. In this work, we present a QSP modeling platform for immuno‐oncology (IO) that incorporates detailed mechanisms for important immune interactions. This modular platform allows for the construction of QSP models of IO with varying degrees of complexity based on the research questions. Finally, we demonstrate the use of the platform through two example applications of immune checkpoint therapy. John Wiley and Sons Inc. 2020-09-07 2020-09 /pmc/articles/PMC7499194/ /pubmed/32618119 http://dx.doi.org/10.1002/psp4.12546 Text en © 2020 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Tutorial
Sové, Richard J.
Jafarnejad, Mohammad
Zhao, Chen
Wang, Hanwen
Ma, Huilin
Popel, Aleksander S.
QSP‐IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno‐Oncology Applications
title QSP‐IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno‐Oncology Applications
title_full QSP‐IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno‐Oncology Applications
title_fullStr QSP‐IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno‐Oncology Applications
title_full_unstemmed QSP‐IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno‐Oncology Applications
title_short QSP‐IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno‐Oncology Applications
title_sort qsp‐io: a quantitative systems pharmacology toolbox for mechanistic multiscale modeling for immuno‐oncology applications
topic Tutorial
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499194/
https://www.ncbi.nlm.nih.gov/pubmed/32618119
http://dx.doi.org/10.1002/psp4.12546
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