期刊
NATURE BIOTECHNOLOGY
卷 33, 期 7, 页码 733-735出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.3212
关键词
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The in vitro potency of antibody-drug conjugates (ADCs) increases with the drug-to-antibody ratio (DAR); however, ADC plasma clearance also increases with DAR, reducing exposure and in vivo efficacy. Here we show that accelerated clearance arises from ADC hydrophobicity, which can be modulated through drug-linker design. We exemplify this using hydrophilic auristatin drug linkers and PEGylated ADCs that yield uniform, high-DAR ADCs with superior in vivo performance.
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