Inducing/expanding Tregs <i>in vivo</i>to suppress autoimmunity using a new bispecific therapeutic containing IL-2 and TGFβ.

Abstract The objective of this study was to test a new injectable therapeutic, CUE-401, that is designed induce Foxp3 expressing Tregs by signaling through both IL-2 and TGFβ receptors. Unlike therapies activate expand existing Tregs, biotherapeutic subsets iTregs from naïve autoreactive CD4 +T cells Tregs. Experiments were performed determine the biological activities CUE-401 in vitro vivo after administering mice with active ongoing autoimmunity. results showed stimulating CD4+ T presence effective at inducing phenotypically functionally indistinguishable iTreg induced recombinant TGFβ. When injected into mice, increasing +Tregs. treated complexes, did not proliferation cells. Single cell RNA sequencing revealed subset shared many transcripts known be expressed TGFβ-induced iTregs. Finally, suppressing organ specific These studies identify approach suppress autoimmunity other inflammatory diseases.