ENGINEERING AN IMMUNOCYTOKINE THAT SELECTIVELY POTENTIATES REGULATORY T CELL ACTIVATION

Regulatory T cells (TRegs) have been shown to play a critical role in autoim-mune disease by suppressing harmful inflammatory responses. The interleukin-2 (IL-2) cytokine has been used to preferentially expandTRegsvia the activationof high-affinity heterotrimeric receptors on the cell surface. However, the ther-apeutic efficacy is limited by off-target complications resulting from expansionof immunostimulatory cells. Previous studies have documented that fusionproteins that link mouse IL-2 to anti-mouse IL-2 antibodies are able to selec-tively target the cytokine toTRegs. We report the generation of a fusion proteinbetween human IL-2 and the anti-human IL-2 antibody F5111, which prefer-entially biasesTRegexpansion in vitro, ex vivo, and in vivo. Collectively, theseresults suggest that the IL-2/F5111 fusion protein harbors great promise as animmunotherapeutic platform to treat autoimmune diseases