Ontology highlight
ABSTRACT:
SUBMITTER: Kang JC
PROVIDER: S-EPMC6668989 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
Nature biotechnology 20190401 5
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 tha ...[more]