Computational analysis of cytokine release following bispecific T-cell engager therapy
Developing a QSP model for prostate cancer immunotherapy
- Area
- Systems Pharmacology
- Expertise
- Modeling & simulation
Challenge
Develop a Quantitative System Pharmacology (QSP) model to evaluate the effect of different immunotherapies in prostate cancer and provide a computational framework to support drug development, by generating hypotheses that can be tested experimentally in pre-clinical models.
What we did
After a comprehensive review of existing mathematical models, we defined a first QSP model of prostate cancer immunotherapy, calibrated using data from pre-clinical experiments. We developed the model by using Ordinary Differential Equations (ODEs) describing the tumor, key components of the immune system, and seven treatments. A second mathematical model has been also developed, which targets human data.
Outcome
The model allows to evaluate the efficacy of numerous combination therapies by considering both the model-predicted degree of tumor inhibition and the predicted synergistic effects. Our simulations predicted cancer vaccine combined with immune checkpoint blockade as the most effective dual-drug combination immunotherapy for subjects treated with androgen-deprivation therapy that developed resistance.
Partner
Publications
Coletti R, Leonardelli L, Parolo S, Marchetti L, A QSP model of prostate cancer immunotherapy to identify effective combination therapies. Scientific Reports 10, Article number: 9063, 2020.
See 10.1038/s41598-020-65590-0
Coletti R, Pugliese A, Marchetti L, Modeling the effect of immunotherapies on human castration-resistant prostate cancer. Journal of Theoretical Biology 509, 2021.
See 10.1016/j.jtbi.2020.110500
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