A CD25-biased interleukin-2 for autoimmune therapy engineered via a semi-synthetic organism.

ABSTRACT:

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. A library of rhIL-2 molecules was constructed with single site-specific, biorthogonal chemistry-compatible non-canonical am

SUBMITTER: Ptacin JL 

PROVIDER: S-EPMC10966033 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature