Reducing hydrophobicity of homogeneous antibody-drug conjugates improves pharmacokinetics and therapeutic index.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26076429.
- Also identified by DOI 10.1038/nbt.3212.
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Abstract
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.
Medical subject headings
- Chemistry, Pharmaceutical
- Immunoconjugates
- Pharmaceutical Preparations