Site-Specific Glycan-Conjugated NISTmAb Antibody Drug Conjugate Standards

Published

July 6, 2021

Author(s)

Brian Agnew, Shanhua Lin, Robert Aggeler, John E. Schiel, Catherine Mouchahoir

Abstract

Antibody drug conjugates (ADCs) represent a rapidly growing modality for the treatment of numerous oncology indications. The complexity of analytical characterization method development is increased due to the potential for synthetic intermediates and process related impurities. In addition, the cytotoxicity of such materials provides an additional challenge with regard to handling products and/or sharing materials with analytical collaborators and/or vendors for technology development. Herein we have utilized a site-specific chemoenzymatic glycoconjugation strategy for preparing ADC mimetics comprised of the NIST monoclonal antibody (NIStmAb) conjugated to non-cytotoxic payloads representing both small molecules and peptides. The materials were exhaustively characterized with high resolution mass spectrometry based approaches to demonstrate the utility each analytical method for confirming the conjugation fidelity as well as deep characterization of synthetic intermediates and impurities arising from intentional payload raw material heterogeneity. These materials therefore represent a widely available test metric to develop novel ADC analytical methods as well a platform to discuss best practices for extensive characterization.

Citation

Analytical Chemistry

Volume

413

Issue

20

Pub Type

Journals

Download Paper

https://doi.org/10.1007/s00216-021-03460-y

Local Download

Keywords

Antibody Drug Conjugate, NISTmAb, monoclonal antibody, biotherapeutic, biopharmaceutical, system suitability

Citation

Agnew, B. , Lin, S. , Aggeler, R. , Schiel, J. and Mouchahoir, C. (2021), Site-Specific Glycan-Conjugated NISTmAb Antibody Drug Conjugate Standards, Analytical Chemistry, [online], https://doi.org/10.1007/s00216-021-03460-y, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=931190 (Accessed October 31, 2025)