Int J Med Sci 2018; 15(11):1118-1128. doi:10.7150/ijms.24460
Drug repurposing: Ibrutinib exhibits immunosuppressive potential in organ transplantation
1. Shenzhen Xenotransplantation Medical Engineering Research and Development Center, Institute of Translational Medicine, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen University School of Medicine, Shenzhen University Health Science Center, Shenzhen, China
2. Shenzhen Longhua District Central Hospital, Shenzhen, China
3. The Department of Anesthesiology, Weifang Medical University, Weifang, China
4. School of Information Science and Engineering, Shandong Agricultural University, Tai'an, China
# These authors contributed equally to the work.
Zhang Q, Chen J, Gao H, Zhang S, Zhao C, Zhou C, Wang C, Li Y, Cai Z, Mou L. Drug repurposing: Ibrutinib exhibits immunosuppressive potential in organ transplantation. Int J Med Sci 2018; 15(11):1118-1128. doi:10.7150/ijms.24460. Available from http://www.medsci.org/v15p1118.htm
Long-term administration of classic immunosuppressants can induce severe adverse effects. The development of novel immunosuppressants confronts great challenges and opportunities. Ibrutinib, an approved drug for B-cell lineages and chronic graft versus host disease (cGVHD), exhibits immunosuppressive efficacy in autoimmune diseases. Ibrutinib's potential as an immunosuppressant in organ transplantation has not been investigated to date. In a xeno-artery patch model ex vivo, ibrutinib inhibited the proliferation of PBMCs (POD 14-42), mainly CD3+CD4+ and CD3+CD8+ T cells ex vivo. The secretion of cytokines (IL-6, IL-2 and IFN-γ) was suppressed in response to ibrutinib. In allo-skin transplantation models, ibrutinib delayed the rejection of grafted skins. Ibrutinib decreased the amount of T/B cells and lymphocyte infiltration. Altogether, ibrutinib exhibited immunosuppressive potential through cytokine regulation and T cell inhibition ex vivo and in vitro. Repositioning of ibrutinib as an immunosuppressant will greatly facilitate novel immunosuppressant development.
Keywords: Ibrutinib, Immunosuppressant, Immune rejection, Allo-transplantation, Xeno-transplantation