[Toxic effects and use of therapeutic monoclonal antibodies].
The extensive use of therapeutic monoclonal antibodies in clinic has shown that toxic effects may occur in patients. Examples such as muromonab (anti-CD3) and recently TGN1412 (anti-CD28) clearly establish that prediction of toxic effects for these targeted therapies is still complex. These undesirable effects can be classified in four categories: cytokine release syndrome, auto-immune diseases, organ toxicity and opportunistic infections. Immunogenicity, which is highly variable depending on the degree of humanization, could also potentially lead to adverse effects due to immune-complexes formation. The recent accident observed with the anti-CD28 TGN1412 has led to the conclusion that the relative confidence in the safety of monoclonal antibodies should be revised. In addition, the prediction of non-clinical models is rather limited and extrapolation of animal results to the human situation should be performed with caution. A better knowledge of the cellular target of the antibodies and of their mechanisms of action and the identification of risk factors (immune cell activation, wide expression of the target...) should improve the clinical safety of these products. .
Pallardy
Marc
M
Université Paris-Sud, Inserm UMR-S 749, toxicologie, Faculté de pharmacie, 92290 Châtenay-Malabry, France. marc.pallardy@u-psud.fr
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000139:chemically induced; D009202:Cardiomyopathies / Q000139:chemically induced; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems; D003875:Drug Eruptions / Q000209:etiology; D004353:Drug Evaluation, Preclinical; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007105:Immune Complex Diseases / Q000139:chemically induced; D007165:Immunosuppression Therapy / Q000009:adverse effects; D051379:Mice; D009894:Opportunistic Infections / Q000209:etiology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D016207:Cytokines