Cancer Immune Control Dynamics (CICD): A clinical data driven model of systemic immunity.

Abstract

e21058 Background: Recent clinical advances in cancer immuno-therapeutics underscore the need for improved understanding of the complex relationship between cancer and the multiple, multi-functional, inter-dependent, cellular and humoral mediators/regulators of the human immune system. This will lead to improvements in the efficacy of existing immune therapies (patient selection; drug combinations) and insight into new therapeutic targets that may significantly reduce the time to new therapeutics discoveries capable of meaningful clinical impacts. Methods: A systems analysis approach (Cancer Immune Control Dynamics, CICD) attempts to identify the differences between systemic immune homeostasis of healthy volunteers versus patients with metastatic malignant melanoma based on serial measurements of a set of conventional peripheral blood biomarkers of immune function (15 cell subsets and 35 cytokines) assessed daily over 7-10 days. The modeling strategy takes aerospace engineering control theory and system identification algorithms to analyze the state of an individual’s immune system based on the biomarkers’ dynamic non-linear oscillatory behaviors. The analysis framework builds on the classical predator-prey equations commonly used to model biological system dynamics. Tens of thousands of biologically possible biomarker interactions are modeled by a set of matrix equations that creates a system interaction model. CICD quantifies the system equations with biomarker values and solves it to measure the interactions. Results: Quantification of thousands of unique biomarker relationships per participant enables classification based on their immune profile rather than their clinical diagnosis and a basis for a visualization of a person’s immunity state. Conclusions: Results provide initial evidence that a model-based analysis of serially collected biomarker data can lead to biological insights into human immunity, of potential benefit in clinical decisions. It is anticipated that CICD-based capabilities will provide tools to specifically address cancer and treatment modulated (immune checkpoint inhibitors) parameters of human immunity, revealing clinically relevant biological interactions.