Harnessing the Therapeutic Potential of ‘Rogue’ Antibodies

Therapeutic antibodies have revolutionized modern medicine. At present, antibodies are successfully used for treatment of diverse human diseases, ranging from cancer to viral infections. All clinically approved antibodies rely on highly specific recognition of their target antigen. Antigen-binding promiscuity, binding to autoantigens, and propensity for self-binding (homophilic interaction) are highly undesirable characteristics of antibody drug candidates. Nevertheless, the immune system of all healthy individuals constantly produces and uses large quantities of antibodies that can be classified as inappropriate for development as drugs. Here, I provide arguments that antibodies with ‘aberrant’ properties have therapeutic potential. They could be useful in certain complex pathological conditions, thus enriching our armamentarium for treatment of human diseases. Therapeutic antibodies have been successfully used for treatment of diverse pathological conditions.Antibodies exert their therapeutic effects through different mechanisms – inhibition of receptor–ligand interactions or induction of innate immune cytotoxic reactions via their constant fragments.Drug development programs exclusively select highly specific antibodies, that is, antibodies that recognize a single disease-associated target.Antibodies with antigen-binding promiscuity, tendency for self-association, or off-target autoreactivity are usually rejected in the early phases of development.The immune system constantly produces promiscuous antibodies, self-binding antibodies, and autoantibodies. These antibodies play important roles in immune defense and in immune regulation.Antibodies with ‘aberrant’ behavior could offer unique opportunities for therapeutic innovations.