Naturally occurring and synthetic constitutive-active cytokine receptors in disease and therapy. (June 2019) - Floss, Doreen M.
Graphical abstract: Highlights: Constitutive-active cytokine receptors are directly linked to human diseases. Gain-of-function cytokine receptors are promising targets to modulate immunotherapeutic strategies. Synthetic biology approaches resulted in gain-of-function cytokine receptors which might be useful for therapeutics. This review gives insight into the field of naturally occurring and synthetic constitutive-active cytokine receptors. Abstract: Cytokines control immune related events and are critically involved in a plethora of patho-physiological processes including autoimmunity and cancer development. Mutations which cause ligand-independent, constitutive activation of cytokine receptors are quite frequently found in diseases. Many constitutive-active cytokine receptor variants have been directly connected to disease development and mechanistically analyzed. Nature's solutions to generate constitutive cytokine receptors has been recently adopted by synthetic cytokine receptor biology, with the goal to optimize immune therapeutics. Here, CAR T cell immmunotherapy represents the first example to combine synthetic biology with genetic engineering during therapy. Hence, constitutive-active cytokine receptors are therapeutic targets, but also emerging tools to improve or modulate immunotherapeutic strategies. This review gives a comprehensive insight into the field of naturally occurring and synthetic constitutive-active cytokine receptors.