Restoring the Balance: Immunotherapeutic Combinations for Autoimmune Disease

May 6, 2014

An article published last week in Disease Models and Mechanisms by Dawn Smilek, MD, PhD, Mario Ehlers, MD, PhD, and Jerry Nepom, MD, PhD, provides a review of mechanisms involved in the disruption of tolerance to self-antigens in autoimmune disease, highlighting where those mechanisms can be targeted as a means of restoring tolerance and durably reversing autoimmune pathology. Given the complexity of pathways that contribute to autoimmune disease, effective and long-lasting treatment will likely require rational combinations of therapeutics that enhance regulatory components of the immune system, while diminishing antigen-specific effectors and the innate immune response. This approach is consistent with the ITN’s recently-launched PAUSE study in psoriasis, which will assess the combination of ustekinumab (anti-IL12/23) to first reduce T effector cells in the skin, followed by abatacept (CTLA-4 Ig) to prevent pathogenic re-activation of repopulating cells by means of co-stimulatory blockade. Other ITN trials in development will similarly use mechanistically-driven combination therapy approaches to tolerance.

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