Biotherapeutics: Challenges and Opportunities for Predictive Toxicology of Monoclonal Antibodies

• Published in: International journal of molecular sciences Vol. 19; no. 11; p. 3685
• Main Author: Johnson, Dale E
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21-11-2018; MDPI
• Subjects: acute phase reactions; Animal models; Animals; anti-drug antibody (ADA); Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal - toxicity; Antigens; Apoptosis; Biological Therapy - methods; Biological Therapy - trends; biomarkers; Cancer therapies; Clinical trials; cytokine release; Cytokines; Drug dosages; Drug therapy; Drug-Related Side Effects and Adverse Reactions - etiology; Drug-Related Side Effects and Adverse Reactions - prevention & control; Enzymes; Epitopes; FDA approval; Humans; immune complex assays; immunogenicity; Infections; Ligands; Monoclonal antibodies; monoclonal antibodies (mAbs); Patients; Pharmacokinetics; Pharmacology; Proteins; R&D; Research & development; Review; Toxicity; Toxicology; Tumor necrosis factor-TNF; Vascular endothelial growth factor; acute phase reactions; cytokine release; biomarkers; monoclonal antibodies (mAbs); anti-drug antibody (ADA); immune complex assays; immunogenicity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19113685

Biotherapeutics are a rapidly growing portion of the total pharmaceutical market accounting for almost one-half of recent new drug approvals. A major portion of these approvals each year are monoclonal antibodies (mAbs). During development, non-clinical pharmacology and toxicology testing of mAbs differs from that done with chemical entities since these biotherapeutics are derived from a biological source and therefore the animal models must share the same epitopes (targets) as humans to elicit a pharmacological response. Mechanisms of toxicity of mAbs are both pharmacological and non-pharmacological in nature; however, standard in silico predictive toxicological methods used in research and development of chemical entities currently do not apply to these biotherapeutics. Challenges and potential opportunities exist for new methodologies to provide a more predictive program to assess and monitor potential adverse drug reactions of mAbs for specific patients before and during clinical trials and after market approval.