When Selectivity Increases Uncertainty: Context‐Dependent Pharmacology in Antibody Drug Development

As antibody therapeutics become increasingly selective and multi-specific, their pharmacological effects depend more strongly on biological context, creating new uncertainties in drug development. In this perspective, we discuss how context-dependent pharmacology complicates preclinical-to-clinical translation, dose optimization, and rational combination therapy selection for antibody drugs. Recognizing context dependence is essential for realizing the full therapeutic potential of highly selective biologics and for advancing a more predictive, mechanism-informed paradigm in antibody drug development.

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Publication Details

Journal
Clinical and Translational Science
Published
2026-04-01
DOI
https://doi.org/10.1111/cts.70556
Primary Topic
Monoclonal and Polyclonal Antibodies Research
Type
article
Field-Weighted Citation Impact
0.00

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article

When Selectivity Increases Uncertainty: Context‐Dependent Pharmacology in Antibody Drug Development

Yanguang Cao, Xiaozhi Liao
Clinical and Translational Science
Monoclonal and Polyclonal Antibodies Research
article

When Selectivity Increases Uncertainty: Context‐Dependent Pharmacology in Antibody Drug Development

Yanguang Cao, Xiaozhi Liao
article en

Abstract

As antibody therapeutics become increasingly selective and multi-specific, their pharmacological effects depend more strongly on biological context, creating new uncertainties in drug development. In this perspective, we discuss how context-dependent pharmacology complicates preclinical-to-clinical translation, dose optimization, and rational combination therapy selection for antibody drugs. Recognizing context dependence is essential for realizing the full therapeutic potential of highly selective biologics and for advancing a more predictive, mechanism-informed paradigm in antibody drug development.

Clinical and Translational ScienceVol. 19(4)
University of North Carolina at Chapel Hill (US)
National Institutes of Health
Openalex Percentile: Top 21%
Monoclonal and Polyclonal Antibodies Research
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