A potent anti-CD70 antibody-drug conjugate combining a dimeric pyrrolobenzodiazepine drug with site-specific conjugation technology.
@article{Jeffrey2013APA, title={A potent anti-CD70 antibody-drug conjugate combining a dimeric pyrrolobenzodiazepine drug with site-specific conjugation technology.}, author={Scott C. Jeffrey and Patrick J. Burke and Robert P. Lyon and David W Meyer and Django Sussman and Martha E. Anderson and Joshua H. Hunter and Chris I Leiske and Jamie B. Miyamoto and Nicole D. Nicholas and Nicole M. Okeley and Russell J. Sanderson and Ivan J. Stone and Weiping Zeng and Stephen J. Gregson and Luke Masterson and Arnaud C. Tiberghien and Philip Howard and David E. Thurston and C L Law and Peter D. Senter}, journal={Bioconjugate chemistry}, year={2013}, volume={24 7}, pages={ 1256-63 } }
A highly cytotoxic DNA cross-linking pyrrolobenzodiazepine (PBD) dimer with a valine-alanine dipeptide linker was conjugated to the anti-CD70 h1F6 mAb either through endogenous interchain cysteines or, site-specifically, through engineered cysteines at position 239 of the heavy chains. The h1F6239C-PBD conjugation strategy proved to be superior to interchain cysteine conjugation, affording an antibody-drug conjugate (ADC) with high uniformity in drug-loading and low levels of aggregation. In…
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