In vitro immunogenicity prediction: bridging between innate and adaptive immunity

Area of Science:

• Immunology
• Pharmacology
• Biotechnology

Background:

• Biotherapeutic administration can trigger antidrug antibody (ADA) development, involving both innate and adaptive immune systems.
• ADAs pose clinical risks, including reduced drug efficacy and adverse events.
• Animal models are unreliable predictors of human immunogenicity.

Purpose of the Study:

• To highlight the critical role of innate and adaptive immune cells in driving immunogenicity.
• To summarize the utility of in vitro assays employing human immune cells for predicting clinical ADA development.

Main Methods:

• Review of existing literature on immunogenicity assessment.
• Focus on in vitro assays utilizing human innate and adaptive immune cells.
• Analysis of methods to assess immune cell responses to biotherapeutics.

Main Results:

• In vitro assays with human immune cells offer a viable alternative to animal models for assessing immunogenicity.
• These assays can reveal cell-mediated immune responses to biotherapeutics.
• Specific methods are available to evaluate immune cell reactions and predict potential ADA formation.

Conclusions:

• Innate and adaptive immune cells are central to biotherapeutic immunogenicity.
• In vitro assays using human immune cells are essential tools for predicting clinical ADA development.
• These assays improve the safety and efficacy assessment of biologic drugs.