Evgeny Metelkin, Antonina Nikitich, Oleg Demin Jr, Oleg Demin
Institute for Systems Biology (Moscow)
Objectives: Immunotherapy is a new class of cancer treatment that works by activation of immune response of patient to fight with tumor. The main aim of this study is to develop a tool facilitating the development new immunotherapies and their combinations.
Methods: A multidisciplinary team developed Immune Response Template (IRT) which represents family of ODE- based models including both models of individual immune cells and integrated simulation platform describing interactions of multiple immune cell types, cancer cells, soluble mediators, cell-cell contact effects (via surface molecules PD-1:PD-L1, CD40:CD40L) etc.
Results: The models was partially calibrated against publicly available in vitro and in vivo data including activation of T helper cells, CD40-ligand effect on dendritic and B cells (see Figure), production of cytokines by immune and cancer cells, half-lives immune cells etc.
Conclusions: IRT recapitulates essential immune response pathways, effect of immune response on tumor and vice versa. IRT will serve as a framework to facilitate understanding of mechanisms of action of different immunotherapies and their effects, predictive biomarkers identification, optimization of regimens and therapies combination, evaluation of new targets and stratification of subjects enrolled in clinical trials.
Reference: PAGE 25 (2016) Abstr 5887 [www.page-meeting.org/?abstract=5887]
Poster: Drug/Disease modeling - Oncology