March 20-21, 2019 | Boston, MA
Applied BioMath Presence
March 20, 2019 | 9:40 AM
Presentation by Dr. John M. Burke, Co-Founder, President and CEO, Applied BioMath
Presentation title: Model Aided Drug Invention Case Study: GITR-mediated T cell dynamics in Mouse Tumor Micro Environment
- Model Aided Drug Invention (MADI) is a mechanistic mathematical modeling approach used to help reduce late state attrition rates, help accelerate the development of premier (or best-in-class) therapeutics and identify potential R&D hurdles.
- In this collaboration, a MADI approach was used to develop and analyze a systems pharmacology model of an anti-GITR (Glucocorticoid-Induced TNFR-Related protein) agonist antibody to predict Treg and Teff dynamics in the tumor microenvironment in two syngeneic mouse models following administration of anti-GITF agonist antibody.
- The model adequately described the time profiles of intratumoral Treg and Teff, captured Teff immune checkpoint, Treg depletion by ADCP, and Teff proliferation and differentiation into cytotoxic T lymphocytes (CTLs). The model also provided a quantitative understanding of the trade-off between maximizing Treg depletion vs. Teff agonism.