Mechanism of action of therapeutic monoclonal antibodies: Promises and pitfalls of in vitro and in vivo assays

• Published in: Archives of biochemistry and biophysics Vol. 526; no. 2; pp. 146 - 153
• Main Authors: Golay, Josée, Introna, Martino
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.10.2012
• Subjects: ADCC; animal models; Animals; Antibodies, Bispecific - pharmacology; Antibodies, Bispecific - therapeutic use; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibody; assays; Cell death; Cell Death - drug effects; Complement; Drug Evaluation, Preclinical - methods; drugs; Humans; Immune System - drug effects; Immunoconjugates - pharmacology; Immunoconjugates - therapeutic use; Immunoglobulin Fragments - pharmacology; Immunoglobulin Fragments - therapeutic use; mechanism of action; monoclonal antibodies; Phagocytosis; Phagocytosis - drug effects; pharmaceutical industry; research and development; screening; testing; toxicity; Complement; Antibody; Cell death; ADCC; Phagocytosis
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2012.02.011

► The major known mechanisms of action of therapeutic mAbs are summarized. ► The methods and problems with cell death and proliferation assays are reviewed. ► The assays and pitfalls of immune mediated activities of antibodies are reviewed. ► Whether in vitro and in vivo assays of antibodies predict clinical efficacy is discussed. Therapeutic monoclonal antibodies (mAbs) are mostly used in cancer, as anti-infectious agents and as immunomodulatory drugs, and are amongst the most active area of research and development in the pharmaceutical industry. This class of drugs comprises unconjugated antibodies or antibody fragments, antibody–drug conjugates, radio-immunoconjugates and bispecific/trispecific molecules. A better understanding of the mechanism of action of successful mAbs is fundamental for the selection of more active and less toxic mAbs of new generation. Furthermore reliable screening of new compounds at an early stage of preclinical development, for both efficacy and toxicity, should allow the selection of the best molecules at an early stage, and improve the rate of success of this class of drugs. Here we review the major methods that are employed for testing the activity of therapeutic mAbs in vitro and in vivo in small animal models and point out to some of the pitfalls in these assays.