期刊
NATURE BIOTECHNOLOGY
卷 37, 期 5, 页码 523-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41587-019-0073-7
关键词
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资金
- Cancer Prevention and Research Institute of Texas (CPRIT) [RP140141]
- National Institute of General Medical Sciences of the National Institutes of Health [R35GM124952]
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(int) 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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