title: An integrated multiplatform bioanalytical strategy for antibody-drug conjugates: a novel case study.
abstract: BACKGROUND
  The bioanalytical strategy for antibody-drug conjugates (ADC) includes numerous measurements integrally designed to provide comprehensive characterization of PK, PD and immunogenicity. This manuscript describes the utilization of reagents specifically tailored to an ADC with a microtubule polymerization inhibitor payload and cathepsin B cleavable linker.
  
  
  METHODS
  The PK strategy includes the evaluation of physiological levels of total antibody, active ADC, total ADC, antibody-conjugated payload and unconjugated payload. These data are evaluated in the context of target and antidrug antibody levels to elucidate bioactive ADC.
  
  
  CONCLUSIONS
  Herein, we discuss how this strategy has been applied and present our preliminary observations. Continuously evolving to meet pipeline demands, the integrated bioanalytical data will provide critical insights into the exposure-response relationship.
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Myler
authors.affiliation: Biologics Discovery California, Bristol-Myers Squibb, Redwood City, CA 95035, USA.
authors.forename: Vangipuram S
authors.initials: VS
authors.lastname: Rangan
authors.affiliation: Bioanalytical Sciences-LCMS, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kozhich
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Cummings
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Neely
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Dail
authors.affiliation: Bioanalytical Sciences-LCMS, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Ang
authors.initials: A
authors.lastname: Liu
authors.affiliation: Drug Safety Evaluation, New Brunswick, NJ, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Wang
authors.affiliation: Exploratory Clinical & Translational Research, Lawrenceville, NJ 08648, USA.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Vezina
authors.affiliation: Drug Safety Evaluation, New Brunswick, NJ, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Freebern
authors.affiliation: Biologics Discovery California, Bristol-Myers Squibb, Redwood City, CA 95035, USA.
authors.forename: Mei-Chen
authors.initials: MC
authors.lastname: Sung
authors.affiliation: Biologics Discovery California, Bristol-Myers Squibb, Redwood City, CA 95035, USA.
authors.forename: David
authors.initials: D
authors.lastname: Passmore
authors.affiliation: Biologics Discovery California, Bristol-Myers Squibb, Redwood City, CA 95035, USA.
authors.forename: Shrikant
authors.initials: S
authors.lastname: Deshpande
authors.affiliation: Biologics Discovery California, Bristol-Myers Squibb, Redwood City, CA 95035, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kempe
authors.affiliation: Bioanalytical Sciences-LCMS, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Huidong
authors.initials: H
authors.lastname: Gu
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Saewert
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Manney
authors.affiliation: Bioanalytical Sciences-LCMS, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: John
authors.initials: J
authors.lastname: Lute
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Zambito
authors.affiliation: Bioanalytical Research, Lawrenceville, NJ 08648, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wong
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Piccoli
authors.affiliation: Bioanalytical Sciences-LCMS, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Aubry
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Renuka
authors.initials: R
authors.lastname: Pillutla
authors.affiliation: Bioanalytical Sciences-LCMS, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Arnold
authors.affiliation: Bioanalytical Sciences-Biologics, Bristol-Myers Squibb, Lawrenceville, NJ 08648, USA.
authors.forename: Binodh
authors.initials: B
authors.lastname: DeSilva
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates