Engineering a HER2-specific antibody–drug conjugate to increase lysosomal delivery and therapeutic efficacy
Copyright policy )Engineering a HER2-specific antibody–drug conjugate to increase lysosomal delivery and therapeutic efficacy
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.
- University of Southampton United Kingdom
- Texas A&M University United States
- Texas A&M University United States
- The University of Texas System United States
- The University of Texas Health Science Center at Houston United States
Cytotoxicity, Immunologic, Immunoconjugates, Cell Survival, Receptor, ErbB-2, 610, Antineoplastic Agents, Breast Neoplasms, Antibodies, Monoclonal, Humanized, Xenograft Model Antitumor Assays, Article, Mice, Drug Delivery Systems, Cell Line, Tumor, Animals, Humans, Female, Lysosomes
Cytotoxicity, Immunologic, Immunoconjugates, Cell Survival, Receptor, ErbB-2, 610, Antineoplastic Agents, Breast Neoplasms, Antibodies, Monoclonal, Humanized, Xenograft Model Antitumor Assays, Article, Mice, Drug Delivery Systems, Cell Line, Tumor, Animals, Humans, Female, Lysosomes
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