[Toxic effects and use of therapeutic monoclonal antibodies]

Area of Science:

• Immunology
• Pharmacology
• Clinical Medicine

Background:

• Therapeutic monoclonal antibodies (mAbs) are widely used but can cause significant toxic effects.
• Examples like muromonab (anti-CD3) and TGN1412 (anti-CD28) highlight the complexity in predicting mAb toxicity.
• Adverse events include cytokine release syndrome, autoimmune diseases, organ toxicity, and infections.

Purpose of the Study:

• To review the complex toxic effects associated with therapeutic monoclonal antibodies.
• To emphasize the limitations of current non-clinical models in predicting human toxicity.
• To suggest improvements for enhancing the clinical safety of monoclonal antibody therapies.

Main Methods:

• Review of clinical data and case studies involving therapeutic monoclonal antibodies.
• Analysis of adverse event classifications and contributing factors.
• Discussion of immunogenicity and its role in adverse effects.

Main Results:

• Monoclonal antibody toxicity is complex and challenging to predict, with diverse adverse effects observed.
• Non-clinical models have limited predictive value for human responses to mAbs.
• Immunogenicity can lead to adverse events through immune-complex formation.

Conclusions:

• The safety of therapeutic monoclonal antibodies requires careful re-evaluation, especially after incidents like the TGN1412 event.
• Improved understanding of cellular targets, mechanisms of action, and risk factors is crucial for safer mAb development.
• Caution is advised when extrapolating animal study results to human clinical scenarios.