Controlling alloimmunity after transplantation remains a significant challenge, as existing immunosuppressive agents typically inhibit both effector T (Teff) and regulatory T (Treg) cells. Using the non-human primate graft-versus-host disease (GVHD) model, Tkachev et al. now demonstrate that the combination of the mTOR inhibitor sirolimus with an antibody against the tumour necrosis factor superfamily member OX40L (KY1005) synergistically controls T cell activation after haematopoietic stem cell transplantation while permitting robust regulatory T cell reconstitution. This results in prolonged GVHD-free survival of more than 100 days.
References
Tkachev, V. et al. Combined OX40L and mTOR blockade controls effector T cell activation while preserving Treg reconstitution after transplant. Sci. Transl Med. 9, eaan3085 (2017)10.1126/scitranslmed.aan3085
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Crunkhorn, S. Combining OX40L and mTOR blockade. Nat Rev Drug Discov 16, 754 (2017). https://doi.org/10.1038/nrd.2017.207
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DOI: https://doi.org/10.1038/nrd.2017.207
