Hydrophobic interaction chromatography (HIC) method development and characterization of resolved drug-load variants in site-specifically conjugated pyrrolobenzodiazepine dimer-based antibody drug conjugates (PBD-ADCs)

2020 ◽  
Vol 179 ◽  
pp. 113027 ◽  
Author(s):  
Thamara Janaratne ◽  
Xiu C. Wang ◽  
Calvin Becker ◽  
Yanqun Zhao ◽  
Rob Leanna ◽  
...  
Keyword(s):  
Hydrophobic Interaction ◽  
Method Development ◽  
Hydrophobic Interaction Chromatography ◽  
Drug Load ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Pyrrolobenzodiazepine Dimer ◽  
Antibody Drug

scholarly journals Application of triple quadrupole mass spectrometry for the characterization of antibody–drug conjugates

2019 ◽  
Vol 411 (12) ◽  
pp. 2569-2576 ◽  
Author(s):  
Malin Källsten ◽  
Matthijs Pijnappel ◽  
Rafael Hartmann ◽  
Fredrik Lehmann ◽  
Lucia Kovac ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Triple Quadrupole ◽  
Quadrupole Mass ◽  
Triple Quadrupole Mass Spectrometry ◽  
Antibody Drug Conjugates ◽  
Quadrupole Mass Spectrometry ◽  
Drug Conjugates ◽  
Antibody Drug

scholarly journals Multilevel characterization of antibody-ligand conjugates by CESI-MS

2020 ◽  
Vol 20 ◽  
Author(s):  
Bryan Fonslow ◽  
Gabor Jarvas ◽  
Marton Szigeti ◽  
Andras Guttman
Keyword(s):  
Mass Spectrometry ◽  
Capillary Electrophoresis ◽  
Peptide Mapping ◽  
Site Occupancy ◽  
Intact Protein ◽  
Ionization Mass ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

Aims: Demonstrating the capabilities of our new capillary electrophoresis – mass spectrometry method, which facilitates highly accurate relative quantitation of modification site occupancy of antibody-ligand (e.g., antibody-drug) conjugates. Background: Antibody-drug conjugates play important roles in medical discovery for imaging and therapeutic intervention. The localization and stoichiometry of the conjugation can affect the orientation, selectivity, specificity, and strength of molecular interactions, influencing biochemical function. Objective: To demonstrate the option to analyze the localization and stoichiometry of antibody-ligand conjugates by using essentially the same method at all levels including ligand infusion, peptide mapping, as well as reduced and intact protein analysis. Materials and Methods: Capillary electrophoresis coupled to electrospray ionization mass spectrometry was used to analyze the antibodyligand conjugates. Results: We identified three prevalent ligand conjugation sites with estimated stoichiometries of 73, 14, and 6% and an average ligand-antibody ratio of 1.37, illustrating the capabilities of CE-ESI-MS for rapid and efficient characterization of antibody-drug conjugates. Conclusion: The developed multilevel analytical method offers a comprehensive way to determine the localization and stoichiometry of antibody-drug conjugates for molecular medicinal applications. In addition, a significant advantage of the reported approach is that small, hydrophilic, unmodified peptides well separated from the neutrals, which is not common with other liquid phase separation methods such as LC.

Synthesis and evaluation of pyrrolobenzodiazepine dimer antibody-drug conjugates with dual β-glucuronide and dipeptide triggers

2019 ◽  
Vol 179 ◽  
pp. 591-607 ◽  
Author(s):  
Stephen J. Gregson ◽  
Allison M. Barrett ◽  
Neki V. Patel ◽  
Gyoung-Dong Kang ◽  
Davide Schiavone ◽  
...  
Keyword(s):  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Pyrrolobenzodiazepine Dimer ◽  
Antibody Drug

scholarly journals Cutting-edge mass spectrometry methods for the multi-level structural characterization of antibody-drug conjugates

2016 ◽  
Vol 13 (2) ◽  
pp. 157-183 ◽  
Author(s):  
Alain Beck ◽  
Guillaume Terral ◽  
François Debaene ◽  
Elsa Wagner-Rousset ◽  
Julien Marcoux ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Structural Characterization ◽  
Cutting Edge ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Multi Level ◽  
Antibody Drug
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