Applications of mechanistic modelling to clinical and experimental immunology: an emerging technology to accelerate immunotherapeutic discovery and development

The application of in silico modelling is starting to emerge as a key methodology to advance our understanding of mechanisms of disease pathophysiology and related drug action, and in the design of experimental medicine and clinical studies. In this perspective, we will present a non-technical discussion of a small number of recent and historical applications of mathematical, statistical and computational modelling to clinical and experimental immunology. We focus specifically on mechanistic questions relating to human viral infection, tumour growth and metastasis, and T-cell activation. These exemplar applications highlight the potential of this approach to impact on human immunology informed by ever expanding experimental, clinical and `omics' data. Despite the capacity of mechanistic modelling to accelerate therapeutic discovery and development and to de-risk clinical trial design, it is not widely utilised across the field. We outline ongoing challenges facing the integration of mechanistic modelling with experimental and clinical immunology, and suggest how these may be overcome. Advances in key technologies including multi-scale modelling, machine learning and the wealth of `omics' datasets, coupled with advancements in computational capacity are providing the basis for mechanistic modelling to impact on immunotherapeutic discovery and development over the next decade