Mass Spectrometry-Based Methodologies for Pharmacokinetic Characterization of Antibody Drug Conjugate Candidates During Drug Development

2017 ◽  
pp. 183-201 ◽  
Author(s):  
Yongjun Xue ◽  
Priya Sriraman ◽  
Matthew V. Myers ◽  
Xiaomin Wang ◽  
Jian Chen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Drug Development ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Antibody Drug

scholarly journals Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine-linked antibody drug conjugate

2015 ◽  
Vol 24 (8) ◽  
pp. 1210-1223 ◽  
Author(s):  
Julien Marcoux ◽  
Thierry Champion ◽  
Olivier Colas ◽  
Elsa Wagner-Rousset ◽  
Nathalie Corvaïa ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ion Mobility ◽  
Native Mass Spectrometry ◽  
Trastuzumab Emtansine ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Antibody Drug

scholarly journals Correction to Comprehensive Middle-Down Mass Spectrometry Characterization of an Antibody–Drug Conjugate by Combined Ion Activation Methods

2020 ◽  
Vol 92 (17) ◽  
pp. 12097-12097
Author(s):  
Eleanor Watts ◽  
Jon D. Williams ◽  
Laura J. Miesbauer ◽  
Milan Bruncko ◽  
Jennifer S. Brodbelt
Keyword(s):  
Mass Spectrometry ◽  
Antibody Drug Conjugate ◽  
Ion Activation ◽  
Drug Conjugate ◽  
Antibody Drug

Comprehensive Middle-Down Mass Spectrometry Characterization of an Antibody–Drug Conjugate by Combined Ion Activation Methods

2020 ◽  
Vol 92 (14) ◽  
pp. 9790-9798 ◽  
Author(s):  
Eleanor Watts ◽  
Jon D. Williams ◽  
Laura J. Miesbauer ◽  
Milan Bruncko ◽  
Jennifer S. Brodbelt
Keyword(s):  
Mass Spectrometry ◽  
Antibody Drug Conjugate ◽  
Ion Activation ◽  
Drug Conjugate ◽  
Antibody Drug

scholarly journals Systematic LC/MS/MS Investigations for the IND-Enabling Extended Characterization of Antibody–Drug Conjugate Modifications

Antibodies ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 40
Author(s):  
Thomas Linz ◽  
Dominick Yeo ◽  
Qiuting Hong ◽  
Wesley Zmolek ◽  
Jesse McFarland ◽  
...  
Keyword(s):  
Small Molecule ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Liquid Chromatography Tandem Mass ◽  
Molecular Components ◽  
Mass Shifts ◽  
Composition Changes ◽  
Antibody Drug

We hypothesized that systematic liquid chromatography-tandem mass spectrometry investigations of an antibody–drug conjugate (ADC), its small and large molecular components, and surrogate small-molecule conjugates might comprise a simple and efficient approach for the extended characterization of ADCs. Furthermore, we envisioned that results from this work might allow us to assign specific composition changes in the ADC based on monoisotopic mass shifts of conjugatable modifications as detected in the surrogate small-molecule conjugates. We tested our hypothesis with a case study using an aldehyde-tag-based ADC conjugated to a noncleavable linker bearing a maytansine payload. Nearly quantitative bioconversion from cysteine to formylglycine was observed in the monoclonal antibody, and bioorthogonal conjugation was detected only on the formylglycine residues in the ADC. Using our method, both conjugatable and nonconjugatable modifications were discovered in the linker/payload; however, only conjugatable modifications were observed on the ADC. Based on these results, we anticipate that our approach to systematic mass spectrometric investigations can be successfully applied to other ADCs and therapeutic bioconjugates for investigational new drug (IND)-enabling extended characterization.

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