Open AccessRuxolitinib, a JAK1/JAK2 selective inhibitor, ameliorates acute and chronic steroid-refractory GvHD mouse models
Author(s) -
Eduardo Huarte,
Michael T. Peel,
Ashish Juvekar,
Philip E. Dubé,
Sarala Sarah,
Lynn Stephens,
Becky Stewart,
Brian Long,
Philip M. Czerniak,
Jean Oliver,
Paul A. Smith
Publication year - 2021
Publication title -
immunotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.127
H-Index - 48
eISSN - 1750-7448
pISSN - 1750-743X
DOI - 10.2217/imt-2021-0013
Subject(s) - ruxolitinib , janus kinase , medicine , hematopoietic stem cell transplantation , graft versus host disease , humanized mouse , stat , immunology , haematopoiesis , cancer research , stat protein , immune system , stat3 , transplantation , signal transduction , stem cell , cytokine , biology , bone marrow , myelofibrosis , biochemistry , genetics
Aim: Graft-versus-host disease (GvHD) is a major complication arising in patients undergoing allogenic hematopoietic stem cell transplantation. Material & methods: We tested ruxolitinib (a selective JAK1/2 inhibitor) efficacy in three different preclinical models of GvHD. Results: Ruxolitinib, at doses that mimic clinically achievable human JAK/signal transducers and activators of transcription target inhibition, significantly reduced alloreactive T-cell activation and infiltration in the lung and skin, leading to improved outcomes in two experimental models of steroid-refractory acute and chronic GvHD. Additionally, we describe a novel humanized GvHD model in which immunodeficient NOG animals are engineered to produce human IL-15 to facilitate enhanced T- and NK cell engraftment, leading to severe GvHD. Conclusion: Ruxolitinib treatment ameliorated disease symptoms resulting from targeted immune modulation via JAK/signal transducers and activators of transcription signaling inhibition.