title: Anti-CD22-MCC-DM1 and MC-MMAF conjugates: impact of assay format on pharmacokinetic parameters determination.
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.
authors.affiliation: Department of Assay and Automation Technology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. stephanj@gene.com
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Stephan
authors.forename: Pamela
authors.initials: P
authors.lastname: Chan
authors.forename: Chien
authors.initials: C
authors.lastname: Lee
authors.forename: Christopher
authors.initials: C
authors.lastname: Nelson
authors.forename: James Michael
authors.initials: JM
authors.lastname: Elliott
authors.forename: Charity
authors.initials: C
authors.lastname: Bechtel
authors.forename: Helga
authors.initials: H
authors.lastname: Raab
authors.forename: David
authors.initials: D
authors.lastname: Xie
authors.forename: Jon
authors.initials: J
authors.lastname: Akutagawa
authors.forename: Jakub
authors.initials: J
authors.lastname: Baudys
authors.forename: Ola
authors.initials: O
authors.lastname: Saad
authors.forename: Saileta
authors.initials: S
authors.lastname: Prabhu
authors.forename: Wai Lee T
authors.initials: WL
authors.lastname: Wong
authors.forename: Richard
authors.initials: R
authors.lastname: Vandlen
authors.forename: Fred
authors.initials: F
authors.lastname: Jacobson
authors.forename: Allen
authors.initials: A
authors.lastname: Ebens
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics*; D006801:Humans; D018796:Immunoconjugates / Q000032:analysis / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics*; D008301:Maleimides / Q000378:metabolism*; D008453:Maytansine / Q000031:analogs & derivatives* / Q000378:metabolism*; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism*; D012680:Sensitivity and Specificity; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D008301:Maleimides; D009842:Oligopeptides; D051918:Sialic Acid Binding Ig-like Lectin 2; C513576:monomethylauristatin F; D008453:Maytansine