Research published in Bone Marrow Transplantation explores the use of the Janus Kinase (JAK) 1 inhibitor itacitinib as a treatment for patients who develop xenogeneic graft versus host disease (xGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HCT). The researchers found that itacitinib decreases human T cell engraftment, increases regulatory T cell (Treg) frequencies, and reduces xGVHD in immunodeficient NSG mice transplanted with human peripheral blood mononuclear cells (hPBMC).
While allo-HCT is a predominant treatment for patients suffering from acute myeloid leukemia, donor T cells from grafts can target patient tissue, resulting in GVHD. The researchers' study used humanized mouse models, whereby hPBMCs were injected into the mice to induce GVHD. Mice subjects were separated into two groups: a control group and an experimental group receiving itacitinib twice daily.
The mice in the experimental group exhibited a median 12-day higher survival rate compared to the mice in the control group (45 days in comparison to 33 days). Additionally, researchers observed that the mice administered itacitinib possessed higher frequencies of human Tregs following allo-HCT as well as decreased numbers of CD8+ T and CD4+ T cells. The authors also found a reduction in graft-versus-leukemia effects when itacitinib was administered. Taken together, these findings provide insight into the way itacitinib reduces xGVHD.
Courtois, J., Ritacco, C., Dubois, S. et al. Itacitinib prevents xenogeneic GVHD in humanized mice. Bone Marrow Transplant (2021).