Anti-cytokine Ab immune therapy: present status and perspectives

Allergy, autoimmunity and the pathogenesis of some chronic diseases are dependent on host innate and adaptative immune responses. Both responses are associated with abnormal cytokine production within pathologic tissues. Over the past two decades, the availability of purified cytokines and cytokine antibodies (Abs) has prompted a therapeutic approach that aims to supply neutralizing Abs against deleterious cytokines, through either passive immunization (administration of large quantities of high affinity Abs, prepared ex vivo) or active immunization (induction of specific Abs, using immunogenic cytokine derivatives). Both passive and active immunization can safely, transiently and effectively be used, as has been documented by animal experimentation and confirmed by clinical trials. Novel anti-cytokine therapeutic compounds, based on passive Ab immunization, are now available to treat rheumatoid arthritis (RA) and have been shown to help control neoangiogenesis in cancer patients. Clinical trials using Abs to treat allergic disorders are also underway. However, the induction of anti-idiotypic Abs may restrict the long-term use of anti-cytokine immunotherapy using allogenic or humanized/chimeric Abs. We propose that greater consideration should be given to active immunization protocols.