(200a) Multi-Scale Modeling in Immuno-Oncology to Support Immunotherapy Drug Development

The innate and adaptive immune responses are complex and encompass a large range of spatial (from molecular interactions to cellular processes and organ functions) and temporal (from milliseconds to minutes and years) scales. Multi-scale modeling of the immune system provides a wholistic view of emergent properties from the dynamic interplay of components across levels of organization. Such models can be used to qualitatively and quantitatively address various immunological questions in support of the development of novel antibody-based constructs and adoptive cellular therapies (e.g., dendritic cell vaccine, chimeric antigen receptor T-cell, and checkpoint therapies). In addition, studying the implications of dynamical interactions between immune cells and cancer cells may provide a basis for discerning individual patient responses to immunotherapy. Multi-scale mathematical models can be utilized to guide hypothesis generation and testing in drug discovery and clinical development in order to discover novel immunotherapeutic targets and rationally design combinatorial treatment strategies. However, there are only a limited number of multi-scale models of immune responses that reach this important goal of providing new insights into the conception, design, and implementation of these promising immunotherapeutic strategies. In this survey, we discuss the current development of multi-scale modeling in immuno-oncology, and in particular, we provide an overview of the current multi-scale models that may be used to identify novel drug targets and combinatorial approaches for the treatment of cancer. A strategic use of multiple model types will be presented.