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Updated: Jan 27, 2026

Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
Published on: September 14, 2018
Engineering a HER2-specific antibody-drug conjugate to increase lysosomal delivery and therapeutic efficacy
Jeffrey C Kang1, Wei Sun1, Priyanka Khare1
1Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX, USA.
Abstract:
We improve the potency of antibody-drug conjugates (ADCs) containing the human epidermal growth factor receptor 2 (HER2)-specific antibody pertuzumab by substantially reducing their affinity for HER2 at acidic endosomal pH relative to near neutral pH. These engineered pertuzumab variants show increased lysosomal delivery and cytotoxicity towards tumor cells expressing intermediate HER2 levels. In HER2int xenograft tumor models in mice, the variants show higher therapeutic efficacy than the parent ADC and a clinically approved HER2-specific ADC.
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