BioCentury
ARTICLE | Distillery Therapeutics

Transplant

January 31, 2017 10:54 PM UTC

Cell culture and mouse studies suggest dual inhibition of AURKA and JAK-2 could help treat GvHD. In co-cultures of human dendritic cells and allogeneic human T cells, a dual inhibitor of AURKA and JAK-2 decreased proliferation of CD4+ and CD8+ T cells compared with the AURKA inhibitor alisertib or a JAK-2 inhibitor tool compound, and increased activation of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1; CD39)-positive Tregs compared with vehicle. In immunodeficient mice receiving transplants of human peripheral blood mononuclear cells (PBMCs), the dual inhibitor decreased expansion of human CD4+ T cells and the ratio of human CD4+ T cells to Tregs, delayed development of GvHD and increased survival compared with vehicle. Next steps could include testing the dual inhibitor in additional models of GvHD...