- Guide to PHARMACOLOGY
Synonyms: aldesleukin | interleukin-2 | Proleukin®
IL-2 is an approved drug (FDA (1992))
Compound class: Endogenous peptide in human, mouse or rat
Comment: IL-2 and IL-15 are cytokines that share common biological effects, but also exhibit distinct, and sometimes competing, functions . Recombinant IL-2 is used clinically with the generic name aldesleukin.
Abbas et al. (2018) have written a review of IL-2 biology and the progress that has been made in developing IL-2 therapeutics .
View more information in the IUPHAR Pharmacology Education Project: interleukin-2
|IL-2 participates in activation-induced cell death (AICD) and maintenance of peripheral CD4+CD25+ regulatory T (Treg) cells , two processes contributing towards the elimination of self-reactive T cells. Treg insufficiency is associated with autoimmune disease, and clinical evaluation of the effects of low dose IL-2 to promote Treg proliferation and function and combat immune inflammatory disorders is showing some promising results . Current IL-2 therapy relies on recombinant peptide that is limited by a short half-life in vivo. To this end, drug developers are working to produce long-acting conjugates with improved pharmackokinetics. Examples include NKTR-358, a PEG-ylated IL-2 analogue that has entered Phase 1 trial in patients with systemic lupus erythematosus (SLE; NCT03556007), and AMG392 (whose recommended INN is efavaleukin alfa), which is an IL-2-IgHG1 Fc fusion protein being developed by Amgen. AMG392 is designed to exhibit improved Treg selectivity compared to aldesleukin. In an alternative strategy, an anti-IL-2 monoclonal antibody code named F5111.2, that binds to IL-2 and stabilizes it in a conformation that induces preferential Treg expansion, has demonstrated immunotherapeutic potential in in vivo models of autoimmune diseases and GvHD . See Abbas et al. (2018) for a review of IL-2 therapeutics and their clinical prospects . Developers of any successful IL-2 agent, whose goal is to boost Treg population and function to treat autoimmune diseases, must ensure that their invention causes minimal effects on the generation of effector and memory cells, natural killer cells, and other innate lymphoid populations that are also under IL-2 regulation, and which could act to negate the desired therapeutic action.|
|US FDA orphan designation only, not approved for this indication.|