| Literature DB >> 27206324 |
Andrew J Bessire1,2,3, T Eric Ballard1,2,3, Manoj Charati1,2,3, Justin Cohen1,2,3, Michael Green1,2,3, My-Hanh Lam1,2,3, Frank Loganzo1,2,3, Birte Nolting1,2,3, Betsy Pierce1,2,3, Sujiet Puthenveetil1,2,3, Lee Roberts1,2,3, Klaas Schildknegt1,2,3, Chakrapani Subramanyam1,2,3.
Abstract
Antibody-drug conjugates (ADC) are currently an active area of research, focused primarily on oncology therapeutics, but also to a limited extent on other areas such as infectious disease. The success of this type of targeted drug delivery is dependent upon many factors, one of which is the performance of the linker in releasing an active drug moiety under the appropriate conditions. As a tool in the development of linker/payload chemistry, we have developed an in vitro method for the identification of payload species released from ADCs in the presence of lysosomal enzymes. This method utilizes commercially available human liver S9 fraction as the source of these enzymes, and this has certain advantages over lysosomal fractions or purified enzymes. This article describes the characterization and performance of this assay with multiple ADCs composed of known and novel linkers and payloads. Additionally, we report the observation of incomplete degradation of mAb protein chains by lysosomal enzymes in vitro, believed to be the first report of this phenomenon involving an ADC therapeutic.Entities:
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Year: 2016 PMID： 27206324 DOI： 10.1021/acs.bioconjchem.6b00192
Source DB: PubMed Journal: Bioconjug Chem ISSN： 1043-1802 Impact factor: 4.774