Physiological Considerations for Modeling in vivo Antibody-Target Interactions

Area of Science:

• Biotechnology
• Pharmacology
• Immunology

Background:

• The pipeline for therapeutic antibodies is expanding, showing higher success rates than small molecules.
• Therapeutic antibodies encounter unique development hurdles, including a translational gap between target affinity and therapeutic effect.

Purpose of the Study:

• To review how local physiological conditions affect antibody-target interactions.
• To highlight the importance of considering physiological factors in antibody development.

Main Methods:

• Literature review of studies examining antibody-target interactions in physiological contexts.
• Analysis of how physical stress, biological fluids, and membrane characteristics influence antibody dynamics.

Main Results:

• Physiological factors like physical stress and biological fluid composition can alter antibody-target association and dissociation rates.
• Tissue microenvironment and physiology critically influence antibody-target interactions, leading to apparent affinity changes.
• These factors impact dynamic target engagement, affecting overall therapeutic effectiveness.

Conclusions:

• Contextualizing antibody-target interactions within physiological conditions is crucial for realizing the full potential of therapeutic antibodies.
• Considering physiological factors early in development aids in rational antibody engineering, preclinical candidate selection, and lead optimization.
• Understanding these influences can bridge the translational gap and improve the success of antibody-based therapeutics.