IL-6 Receptor Blockade but Not IL-2 Treatment Contributes to Long Term NHP Cardiac Allograft Survival in Transient Mixed Chimeras

Targeting IL-6 to prevent cardiac allograft rejection

“…In preliminary studies, NHPs undergoing mixed chimerism that received combined anti‐IL‐6R therapy (tocilizumab) and low‐dose IL‐2 experienced significant T reg expansion with a marked increase in the percentage of peripheral T regs compared to pre‐transplant baseline. However, all treated recipients rejected their heart allografts due to ACR and AMR 68 ,69 . Failure to achieve prolonged heart allograft survival by combining low‐dose IL‐2 with anti‐IL‐6R therapy may have resulted from IL‐2‐induced T cell alloreactivity, as IL‐2 can promote either immune activation or downregulation in a dose‐dependent fashion with a narrow therapeutic window 67 .…”

“…However, all treated recipients rejected their heart allografts due to ACR and AMR. 68,69 Failure to achieve prolonged heart allograft survival by combining low-dose IL-2 with anti-IL-6R therapy may have resulted from IL-2-induced T cell alloreactivity, as IL-2 can promote either immune activation or downregulation in a dose-dependent fashion with a narrow therapeutic window. 67 Therefore, another preliminary group of NHP recipients was treated with anti-IL-6R mAb therapy alone as part of a mixed chimerism-based protocol.…”