Immunotoxicity of monoclonal antibodies

Figures & data

Table 1 The four categories of immunotoxic effects and associated adverse clinical consequences

Immunosuppression	Immunostimulation	Hypersensitivity	Autoimmunity
Infectious complications (*)	Acute reactions related to cytokine release (*)	Anaphylaxis (*)	Systemic autoimmune reactions (*)
Virus-induced neoplasias (*)	More frequent auto-immune diseases (*)	Immune-complex mediated reactions (*)	Organ specific autoimmune reactions
	More frequent allergies to unrelated allergens
	Inhibition of CYP450-dependent pathways

Clinical consequences previously described with mAbs are denoted (*).

Table 2 Main guidelines specifically applicable to the non-clinical safety evaluation of mAbs

ICH S6 Guideline on the Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals (1997; revision ongoing)

US FDA Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use (1997)

EMEA Guideline on Immunogenicity Assessment of Biotechnology-Derived Therapeutic Proteins (2007)

EMEA Guideline on the Strategies to Identify and Mitigate Risks for First-in-Human Clinical Trials with Investigational Medicinal Products (2007)