Jerod L Ptacin, Lina Ma, Carolina E Caffaro, Nicole V Acuff, Kristine Germar, Peter Severy, Yanyan Qu, Jose-Luis Vela, Xinming Cai, Kristine M San Jose, Hans R Aerni, David B Chen, Ean Esche, Taylor K Ismaili, Rob Herman, Yelena Pavlova, Michael J Pena, Jasmine Nguyen, Lilia K Koriazova, Laura K Shawver, Ingrid B Joseph, Jill Mooney, Mark Peakman, Marcos E Milla
BACKGROUND: Natural cytokines are poorly suited as therapeutics for systemic administration due to suboptimal pharmacological and pharmacokinetic (PK) properties. Recombinant human interleukin-2 (rhIL-2) has shown promise for treatment of autoimmune (AI) disorders yet exhibits short systemic half-life and opposing immune responses that negate an appropriate therapeutic index. METHODS: A semi-synthetic microbial technology platform was used to engineer a site-specifically pegylated form of rhIL-2 with enhanced PK, specificity for induction of immune-suppressive regulatory CD4 + T cells (Tregs), and reduced stimulation of off-target effector T and NK cells...
March 26, 2024: Commun Med (Lond)