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- W2186355595 abstract "CONTENT: BACKGROUND Mechanistic models capable of integrating datasets from the molecular, cellular, and tissue level to provide research predictions of tumor response are well-positioned to play a central role in translational research and clinical development for the emerging immuno-oncology therapeutic paradigm. The availability of calibration and validation data from clinical trials from the first successful immuno- oncology therapies such as ipilimumab and nivolumab (including CA184004, MDX1106-03, CA209004, CA209009) facilitates comparison of the simulated outcomes with clinical data. METHODS A multidisciplinary team developed the biological scope of a mechanistic, ODE-based simulation platform. The initial platform focuses on the interactions of multiple immune cell types, cancer cells, soluble mediators, cell-cell contact effects, as well as ipilimumab and nivolumab therapies within the microenvironment of a prototypical simulated lesion and effect on tumor shrinkage. RESULTS The platform was calibrated, taking into account nivolumab and ipilimumab plasma concentrations, circulating absolute lymphocyte counts, trends in tumor cytokines, an IFNγ gene expression signal, changes in tumor infiltrating lymphocytes, and lesion size data. In agreement with clinical observations, an enhancement in lesion response was observed with the combination therapy. CONCLUSION" @default.
- W2186355595 created "2016-06-24" @default.
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- W2186355595 date "2015-01-01" @default.
- W2186355595 modified "2023-09-27" @default.
- W2186355595 title "Title: DEVELOPMENT OF A QUANTITATIVE SYSTEMS PHARMACOLOGY PLATFORM TO SUPPORT TRANSLATIONAL RESEARCH AND CLINICAL DEVELOPMENT IN IMMUNO-ONCOLOGY" @default.
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