A long-lived IL-2 mutein that selectively activates and expands regulatory T cells as a therapy for autoimmune disease.

ABSTRACT: Susceptibility to multiple autoimmune diseases is associated with common gene polymorphisms influencing IL-2 signaling and T_reg function, making T_reg-specific expansion by IL-2 a compelling therapeutic approach to treatment. As an in vivo IL-2 half-life enhancer we used a non-targeted, effector-function-silent human IgG1 as a fusion protein. An IL-2 mutein (N88D) with reduced binding to the intermediate affinity IL-2Rβγ receptor was engineered with a stoichiometry of two IL-2N88D molecules per IgG, i.e. IgG-(IL-2N88D)₂. The reduced affinity of IgG-(IL-2N88D)₂ for the IL-2Rβγ receptor resulted in a T_reg-selective molecule in human whole blood pSTAT5 assays. Treatment of cynomolgus monkeys with single low doses of IgG-(IL-2N88D)₂

SUBMITTER: Peterson LB 

PROVIDER: S-EPMC6284106 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature