Engineering a HER2-specific antibody–drug conjugate to increase lysosomal delivery and therapeutic efficacy View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-04-01

AUTHORS

Jeffrey C. Kang, Wei Sun, Priyanka Khare, Mostafa Karimi, Xiaoli Wang, Yang Shen, Raimund J. Ober, E. Sally Ward

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. More... »

PAGES

1-4

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41587-019-0073-7

DOI

http://dx.doi.org/10.1038/s41587-019-0073-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113160901

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30936563


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