Clinical Immunotoxicology.

Assessment of the potential for a test article to have adverse effects on immune function can be difficult in clinical trials due to a relative lack of useful endpoints. It is therefore common to use a weight of evidence approach with nonclinical studies to indicate if there is a cause for concern that the test article has immunotoxic potential. The most commonly used follow-up assay for immunosuppression is the T-dependent antibody response (TDAR). However, final selection of an assay (or assays) to evaluate potential human immunotoxicity depends on the type of findings in nonclinical studies. For example, signs of unintended immunostimulation or immunomodulation may be assessed using specialized assays using human cells. Other factors should also be considered, such as pharmacology of the test article, potential structural similarities with known immunomodulatory agents, and/or pharmacokinetic/drug disposition findings consistent with accumulation of test article/metabolite in immune system tissues. Although evaluation of the potential for a test article to have adverse effects on immune function can be a complex task, established nonclinical models and some clinical endpoints can be useful to determine the safety of products intended for use as human therapeutics.