An In Vitro Human Skin Test for Predicting Skin Sensitization and Adverse Immune Reactions to Biologics

Area of Science:

• Immunology
• Pharmacology
• Dermatology

Background:

• Biologics, including monoclonal antibodies (mAbs), are effective therapeutics for various conditions.
• A significant risk associated with biologics is immune-mediated adverse drug reactions.
• Predicting these reactions pre-clinically is crucial for patient safety.

Purpose of the Study:

• To introduce and validate a novel human in vitro skin explant test.
• To assess the test's ability to predict skin sensitization and adverse immune reactions to therapeutic antibodies.
• To correlate in vitro findings with clinical outcomes of monoclonal antibody treatments.

Main Methods:

• Utilized a human in vitro skin explant model.
• Assessed immune responses via T cell proliferation and multiplex cytokine analysis.
• Evaluated skin damage through histopathological analysis (Grades I-IV).

Main Results:

• The skin explant test demonstrated significant increases in T cell proliferation in positive response groups (p < 0.004).
• Elevated levels of key cytokines (IFNγ, TNFα, IL-10, IL-12, IL-13, IL-1β, IL-4) were observed in positive response groups (p < 0.0001 to p < 0.004).
• The assay correctly predicted clinical outcomes for 13 out of 16 therapeutic monoclonal antibodies (correlation coefficient = 0.770, p = 0.0001).

Conclusions:

• The human in vitro skin explant test is a valuable pre-clinical tool.
• The assay effectively predicts adverse immune reactions, including skin sensitization.
• It accurately identifies T cell proliferation and cytokine release associated with monoclonal antibody adverse events.