Cytokines as clinical adjuvants: how far are we?

In spite of the explosive growth in the discovery of cytokines and chemokines and in the understanding of their modes of action, clinical use of such agents as adjuvants has been primarily restricted to patients with cancer or chronic viral infections suffering from various levels of immune impairment and for whom the chemotherapeutic armamentarium, as well as other forms of immunotherapy, have been exhausted. This cautious approach has been justified by the difficulties inherent to the biological function and delivery of such pleiotropic agents, where doses needed to achieve the targeted immune enhancement often result in serious side effects, especially during systemic administration. In addition, optimization of dosages, administration schedules and biological effects in humans often do not correlate well with preclinical data derived from animal models. Nevertheless, novel preventive immunization strategies that target a precise type of immune response in immunocompetent individuals are expected to greatly benefit from the incorporation of cytokines and chemokines. This review provides an overview of current clinical administration of cytokines as well as a description of select Phase I testing of new agents designed to enhance immune defenses in vivo.