Engineering a HER2-specific antibody-drug conjugate to increase lysosomal delivery and therapeutic efficacy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30936563.
- Also identified by DOI 10.1038/s41587-019-0073-7 and PMC identifier 6668989.
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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 HER2<sup>int</sup> xenograft tumor models in mice, the variants show higher therapeutic efficacy than the parent ADC and a clinically approved HER2-specific ADC.
Medical subject headings
- Antibodies, Monoclonal, Humanized
- Breast Neoplasms
- Drug Delivery Systems
- Immunoconjugates
- Erb-b2 Receptor Tyrosine Kinases