Title: siRNA therapy for ex vivo treatment of stem cell grafts and/or donor lymphocytes
Allogeneic T cells represent the most potent treatment for hematopoietic malignancies such es leukemia. However, after interaction with host antigen-presenting cells, T cells can lead to the unwanted Graft-versus-Host Disease (GvHD) or the desired Graft-versus-Leukemia (GvL) effect. In contrast to currently available GvHD drugs, not being able to differentiate between GvH and GvL, we want to change the phenotype of T cells using siRNAs to prevent development of GvHD, while preserving GvL. Here, we show a siRNA mix inhibiting different target genes as a therapeutic concept. The siRNA mix holds promise to prevent GvH while preserving GvL effect of T cells and is the first proof-of-principle for siRNA therapy to modulate GvHD.