A Systems Pharmacology Approach to Immunogenicity

Predicting incidence of clinical immunogenicity is currently challenging, due to the intrinsic complexity of the immune system and the involvement of various risk factors. To help address the challenge, we have developed a mechanistic, multi-scale mathematical model, by recapitulating fundamental biological mechanisms. The key strength of this systems model lies in its capacity to integrate various risk factors, e.g., T- and B- epitopes, patients’ HLA background, naïve T and B cell numbers, into the underlying biology. The model can simulate the immune response at both individual and population level, and provides many clinical-relevant predictions, e.g., incidences for immunogenicity and loss of efficacy. An example of simulating human population immune responses against a therapeutic protein will be provided, to illustrate potential applications in drug development. The current model can be subjected to rigorous experimental validation, and could eventually serve as a tool to integrate various preclinical and clinical results for immunogenicity prediction and mitigation.