Monoclonal antibodies for prophylaxis and therapy of infectious diseases.
Monoclonal antibodies (mAb) are attractive biologic drugs due to their exquisite specificity and well understood mechanisms of action, which results in a higher predictability and lower attrition rate compared with other drugs. Therefore, it may seem surprising that only a single mAb is presently marketed for an infectious disease indication. However, the antibiotic resistance crisis, emerging viral diseases and bioterroristic threats have recently spurred the development of anti-infective mAbs, of which more than a dozen are being tested in clinical trials. Conceptually, and validated in many preclinical models, mAbs will be most effective when used prophylactically against acute viral infections and bacterial toxins. The acute bacterial and chronic viral infections, which are medically and economically far more important, are much more difficult to control by antibodies, as the recent clinical failure of some polyclonal antibody products has shown. In these situations, the synergistic action of two or more mAbs together with a small molecule drug will most likely be required for therapeutic efficacy. This review aims to highlight the scientific and economic opportunities and obstacles that are encountered in the quest to add mAbs to the armament of anti-infective drugs.
ter Meulen
Jan
J
Infectious Diseases, Crucell Holland BV, P.O. Box 2048, 2301, CA Leiden, The Netherlands. j.termeulen@crucell.com
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D002986:Clinical Trials as Topic; D015195:Drug Design; D004345:Drug Industry; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D009181:Mycoses / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D014777:Virus Diseases / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control / Q000821:virology
D000911:Antibodies, Monoclonal; D007155:Immunologic Factors