Research ArticleTransplantation

Targeting Aurora kinase A and JAK2 prevents GVHD while maintaining Treg and antitumor CTL function

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Science Translational Medicine  11 Jan 2017:
Vol. 9, Issue 372, eaai8269
DOI: 10.1126/scitranslmed.aai8269

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Guiding T cells to stem GVHD

Donor T cell–mediated graft-versus-host disease (GVHD) is a serious complication of stem cell transplantation, but complete inhibition of T cell activation might leave the patient susceptible to leukemia relapse. Betts et al. targeted two kinases involved in T cell costimulation and cytokine-responsiveness to blunt T cell responses. Dual targeting drove human CD4 T cells to become potently suppressive T regulatory cells instead of TH17 effector cells and also prevented GVHD in a humanized mouse model. CD8 T cells were capable of activation after a tumor challenge, indicating that patients receiving this treatment might be able to mount antileukemia responses.