Immunotoxicology IV—Innovative Methods and Applications for Risk Assessment in Pharmaceutical Development: Introduction to the Conference

On September 18–19, 2006, Pharmaceutical Education Associates (PEA) presented the fourth in a series of conferences addressing specific topics in Immunotoxicology. While the working topic of this meeting was innovative methods and applications for risk assessment in pharmaceutical development, the focus of the meeting was more specific to the measurement and evaluation of adverse immunostimulation, particularly as a consequence of treatment with biopharmaceuticals.

While it has long been recognized that toxicity to the immune response can take many forms, including adverse immunostimulation, this topic has generally not been as well-defined as immunosuppression (House and Hastings, 2004). Immunotoxicology IV brought together a diverse group of experts from industry, academia, and the government to examine the concept of Immunotoxicology resulting from either intentional or unintentional therapeutic treatments in humans.

The conference was preceded by a half-day workshop on the immunotoxicology of biopharmaceuticals. This workshop included presentations on the utility of testing human biologicals in animal host resistance assays (Dr. Gary Burleson), identifying hazards and assessing risks associated with biologics intended to target the human immune system (Dr. Andrea Weir), methods and approaches for assessing immunomodulation in nonhuman primates (Dr. Jeanine Bussiere), and techniques and approaches for using immunohistochemistry to measure tissue cross-reactivity (Dr. Noël Dybdal). This unprecedented combination of topics provided the attendees with an excellent working background on how the immunological effects of biopharmaceuticals can be assessed in animals, and how (hopefully) those results can be bridged to humans.

Much of Day 2 of the conference focused on understanding how immunotherapeutics might stimulate the immune system. Specific areas covered this day included an examination of when exaggerated pharmacodynamics becomes immunotoxic (Dr. Dan Wierda), the phenomenon of first dose cytokine release syndrome following monoclonal antibody administration (Dr. Mark Wing), a discussion of how Toll-like receptors stimulate immunity (Dr. Arthur Krieg), and a review of adverse events following IL-17 or IL-23 administration (Dr. Chen Dong). With this comprehensive review of how various immunomodulators act on the immune system, a panel discussion on the adverse consequences of immunostimulation sought to integrate the various mechanisms of action, as well as to suggest potential strategies and techniques for assessing and—more challenging—predicting toxicity of these therapeutics (an excellent review of this panel discussion by Dr. Rafael Ponce is included in this issue). While this discussion, which included valuable audience input, was informative, it was clear that a tremendous amount of work remains to be done before hazard identification and risk assessment of adverse immunostimulation can reach the level of detail that immunosuppression (and, to a limited degree, even hypersensitivity and autoimmunity) currently holds.

The conference concluded with a “hot topics” wrap up including a presentation on identifying biomarkers for stress response (Dr. Stephen Pruett), and a timely update on perinatal exposure and later-life immunotoxic risk (Dr. Rodney Dietert).

Immunotoxicology IV was a highly successful episode in this series of conferences sponsored by PEA, and was notable for including one of the first comprehensive discussions on the increasingly important topic of adverse immunostimulation.