Active and passive anticytokine immune therapies: current status and development

Anticytokine (AC) immune therapies derived from vaccine procedures aim at enhancing natural immune defense mechanisms ineffective to contain abnormally produced cytokines and counteract their pathogenic effects. Given their short half-life, cytokines, the production of which by effector immune cells (T and B lymphocytes, antigen-presenting cells (APCs), natural killer (NK) and endothelial cells) is inducible and controlled by negative feedback regulation, (1) exert locally their signaling to paracrine/autocrine target responder cells carrying high-affinity membrane receptors and (2) are commonly present at minimal concentration in the body fluid (lymph, serum). Aberrant signaling triggered by cytokines, uncontrolly released by effector immune cells or produced by cancer and other pathologic cells, contribute to the pathogenesis of chronic diseases including cancer, viral infections, allergy, and autoimmunity. To block these ectopic cytokine signaling and prevent their pathogenic effects, AC Abs supplied either by injections (passive AC immune therapy) or elicited by immunization with cytokine-derived immunogenes called Kinoids (active AC immune therapy) proved to be experimentally effective and safe. In this review, we detailed the rationale and the requirements for the use of AC immunotherapies in humans, the proof of efficacy of these medications in animal disease models, and their current clinical development and outcome, including adverse side effects they may generate. We particularly show that, to date, the benefit:risk ratio of AC immune therapies is highly positive.