Anti-CD22-MCC-DM1 and MC-MMAF Conjugates: Impact of Assay Format on Pharmacokinetic Parameters Determination

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...

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Bibliographic Details
Published in:Bioconjugate chemistry 2008-08, Vol.19 (8), p.1673-1683
Main Authors: Stephan, Jean-Philippe, Chan, Pamela, Lee, Chien, Nelson, Christopher, Elliott, James Michael, Bechtel, Charity, Raab, Helga, Xie, David, Akutagawa, Jon, Baudys, Jakub, Saad, Ola, Prabhu, Saileta, Wong, Wai Lee T, Vandlen, Richard, Jacobson, Fred, Ebens, Allen
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - analysis
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - metabolism
Antibodies, Monoclonal - pharmacokinetics
Biochemistry
Humans
Immunoconjugates - analysis
Immunoconjugates - immunology
Immunoconjugates - metabolism
Immunoconjugates - pharmacokinetics
Impact analysis
Kinetics
Maleimides - metabolism
Maytansine - analogs & derivatives
Maytansine - metabolism
Mice
Oligopeptides - metabolism
Rodents
Sensitivity and Specificity
Sialic Acid Binding Ig-like Lectin 2 - immunology
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Summary: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.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc800059t