Safety assessment of immunomodulatory biologics: The promise and challenges of regulatory T-cell modulation

Regulatory T-cell (T_reg) modulation is developing as an important therapeutic opportunity for the treatment of a number of important diseases, including cancer, autoimmunity, infection, and organ transplant rejection. However, as demonstrated with IL-2 and TGN-1412, our understanding of the complex immunological interactions that occur with T_reg modulation in both non-clinical models and in patients remains limited and appears highly contextual. This lack of understanding will challenge our ability to identify the patient population who might derive the highest benefit from T_reg modulation and creates special challenges as we transition these therapeutics from non-clinical models into humans. Thus, in vivo testing in the most representative animal model systems, with careful progress in the clinic, will remain critical in developing therapeutics targeting T_reg and understanding their clinical utility. Moreover, toxicology models can inform some of the potential liabilities associated with T_reg modulation, but not all, suggesting a continued need to explore and validate predictive models.