Preclinical and clinical studies have significantly advanced the understanding of the pathophysiology of chronic graft-versus-host disease (GVHD), resulting in new immunomodulatory agents targeting innate immunity, early T-cell activation and signaling, T-cell migration, regulatory T cells, and B cell dysregulation.
This review focuses on 3 recently identified therapeutic targets for chronic GVHD control (IL-17, CSF-1 and Janus kinases (JAKs)), and the immunomodulatory agents developed to inhibit, neutralize, block or impair these targets.
Advances in clinical development that have come about through human trials have shown an acceptable toxicity profile in agents such as brodalumab (anti-IL-17 blocking agent), ixekizumab (anti-IL-17 receptor A), ruxolitinib (JAK1 and JAK2 inhibitor), ibrutinib (BTK and ITK inhibitor), and fostamatinib and entospletinib (Syk inhibitors).
The reviewers conclude that recent advances in the understanding of the immunobiology of chronic GVHD “places the field in an exciting position where strategically targeted therapeutics for the prevention and treatment of chronic GVHD are becoming a reality.”
Betts BC, et al. Biol Blood Marrow Transplant