Biology of IL-2 and its therapeutic modulation: Mechanisms and strategies

Abstract

Cytokines signal through specific cell surface receptors to broadly regulate immune development, differentiation, proliferation, and survival, thereby influencing cellular fate and function. Accordingly, cytokines are potential therapeutic targets for modulation of immune responses. Indeed, over the last several decades, an increasing number of cytokine-based clinical trials have been performed, collectively using either recombinant forms of cytokines or blocking agents that modulate the actions of cytokines. The pleiotropic actions of cytokines, including their abilities to mediate both inflammatory and protective immune responses, indicate that using or targeting cytokines can have desired but also potentially undesirable effects. Here, we focus on the immunomodulatory cytokine, IL-2. We review the underlying basic science related to IL-2 and its biologic actions, discuss the current state of IL-2-based immunotherapy, and focus on emerging concepts of modulating the activities of this cytokine, including the generation of novel partial cytokine agonists as new potential therapeutics.

Keywords: IL-2; STAT5; immunotherapy; partial agonists; γc family cytokines.