PanTreg: A Cell-therapy, System-biology - Based Approach for Therapy of Autoimmunity

Abstract Text: Current efforts for CarTreg are mostly focused on engineering patient’s Treg specific for a single antigen, deemed relevant for the etiopathogenesis of the disease, These approaches have inherent imitations.
We have engineered a first in class lentivirus (PanTreg herein) which: a) binds specifically pro-inflammatory cytokines such as TNF and IFN; b) upon binding, induces expression of FoxP3, TGFb and IL-10 in transfected human polyclonal T cells. We have developed and validated this construct in vitro and found that PanTreg are superior to Treg in regulating human T effector function
We have tested PanTreg in in vivo in a humanised model of GVHD and found that: i) home to microenvironments where inflammatory cytokines are present, and ii) are induced by such inflammatory cytokines in producing locally tolerogenic cytokines, thus inducing immune tolerance, with an effective clinical control based on the induction of active immune tolerance. Indeed, we tested two different does of PanTreg and compared their efficacy against autologous polyclonal, untransduced Treg. No animals died in the experimental arm treated with teh highest dose of PanTreg (p < 0.001 vs control)
In conclusion, we describe here our initial experience with a first in class type of CarTreg, where the scFv is specific for an inflammatory cytokine. This approach has the potential to provide with a single construct an innovative approach, and perhaps a permanent solution, to many diseases, in which such cytokines are relevant, by inducing active tolerance rather than suppressing, or “sponging out” the relevant cytokine