Translational challenges of immunotoxicity assessments

Predicting the potential of biopharmaceuticals to induce adverse immunologic events has become increasingly complex due to the diversity of treatment modalities and their structural complexity. Furthermore, unintentional or unexpected effects on immune homeostasis may manifest secondary to intended pharmacology. The potential of therapeutics to induce long-lasting adverse effects on the immune system has spurred the drug development community to continuously evaluate scientific practices used to assess liabilities. This article will explore the translational potential of the state-of-the-art immunotoxicology assessments performed in non-clinical species to inform clinical benefit/risk assessments and develop meaningful clinical risk monitoring or mitigation plans. Examples of high impact challenges faced in the translation of immunotoxicity signals from animals to humans and subsequent actions taken based on a deep understanding of the immunobiology of the biopharmaceutics will be highlighted in three case studies.