| Literature DB >> 18637680 |
Jean-Philippe Stephan1, Pamela Chan, Chien Lee, Christopher Nelson, James Michael Elliott, Charity Bechtel, Helga Raab, David Xie, Jon Akutagawa, Jakub Baudys, Ola Saad, Saileta Prabhu, Wai Lee T Wong, Richard Vandlen, Fred Jacobson, Allen Ebens.
Abstract
CD22 represents a promising target for antibody-drug conjugate therapy in the context of B cell malignancies since it rapidly internalizes, importing specifically bound antibodies with it. To determine the pharmacokinetic parameters of anti-CD22-MCC-DM1 and MC-MMAF conjugates, various approaches to quantifying total and conjugated antibody were investigated. Although the total antibody assay formats gave similar results for both conjugates, the mouse pharmacokinetic profile for the anti-CD22-MCC-DM1 and MC-MMAF appeared significantly different depending on the conjugated antibody assay format. Since these differences significantly impacted the PK parameters determination, we investigated the effect of the drug/antibody ratio on the total and conjugated antibody quantification using multiple assay formats. Our investigations revealed the limitations of some assay formats to quantify anti-CD22-MCC-DM1 and MC-MMAF with different drug load and in the context of a heterogeneous ADC population highlight the need to carefully plan the assay strategy for the total and conjugated antibody quantification in order to accurately determine the ADC PK parameters.Entities:
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Year: 2008 PMID： 18637680 DOI： 10.1021/bc800059t
Source DB: PubMed Journal: Bioconjug Chem ISSN： 1043-1802 Impact factor: 4.774