IFN-a2- and PD-L1-overexpressing T cells (ap-T cells) inhibit graft-versus-host disease but retain anti-leukemia activity in mice

Living cell therapy for immune regulation could achieve long-lasting effects and provide a more nuanced regulatory activity. However, novel approaches that can produce immune regulatory cells, which can robustly expand in culture, persist in vivo after infusion, and sustain immune modulatory function in vivo, remain an unmet need.

Here, we demonstrate that IFN-a2- and PD-L1-overexpressing human T cells (ap-T cells) have a potent capacity to inhibit xenogeneic GVHD (x-GVHD) but preserve the ability to eliminate human xenograft leukemia in NOD/SCID/IL2Rg−/− (NSG) mice. In culture, these CD4+ ap-T cells robustly expanded and stably maintained expression of PD-L1 and IFN-a during expansion. These properties allowed generation of adequate number of immune suppressor cells without large-scale purification for the therapy purpose.