In this white paper, we discuss the application of predictive immunotoxicology and its use as a tool to evaluate risks generated by both enhanced on-target effects (i.e., exaggerated pharmacology) and unexpected risks due to unanticipated pharmacology or off-target activities.

Generally applied to large molecule immunomodulatory therapeutics, these approaches can also be applied in the small molecule space. For example, one can use predictive immunotoxicology assays to de-risk the backbone modifications of oligonucleotide therapeutics or to assess the actions of small molecule therapeutics with immunomodulatory activity.

Predictive immunotoxicology assay selection should be based on the mechanism of action of the therapeutic. These tools can be used as a component of a comprehensive risk assessment for both new therapeutic targets and established modalities. There are a broad range of immune targets and accompanying assays which can be employed to evaluate and predict the immunotoxicologic potential of a therapeutic. This paper broadly discusses the rationale of these approaches with the use of cytokine release assays (CRA) as an example for more detailed discussion.