IMR Press / FBL / Volume 27 / Issue 11 / DOI: 10.31083/j.fbl2711301
Open Access Review
Antibody-Drug Conjugates Targeting Tumor-Specific Mucin Glycoepitopes
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1 School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
2 Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
*Correspondence: (Kelly M. McNagny)
Academic Editors: Brian A. Mendelsohn, Yutaka Matsuda and Josef Jampílek
Front. Biosci. (Landmark Ed) 2022, 27(11), 301;
Submitted: 16 July 2022 | Revised: 8 October 2022 | Accepted: 10 October 2022 | Published: 4 November 2022
(This article belongs to the Special Issue Antibody Drug Conjugates)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Finding the ideal epitope to target is a key element for the development of an antibody-drug conjugate (ADC). To maximize drug delivery to tumor cells and reduce side effects, this epitope should be specific to cancer cells and spare all normal tissue. During cancer progression, glycosylation pathways are frequently altered leading to the generation of new glycosylation patterns selective to cancer cells. Mucins are highly glycosylated proteins frequently expressed on tumors and, thus, ideal presenters of altered glycoepitopes. In this review, we describe three different types of glycoepitopes that are recognized by monoclonal antibodies (mAb) and, therefore, serve as ideal scaffolds for ADC; glycan-only, glycopeptide and shielded-peptide glycoepitopes. We review pre-clinical and clinical results obtained with ADCs targeting glycoepitopes expressed on MUC1 or podocalyxin (Podxl) and two mAbs targeting glycoepitopes expressed on MUC16 or MUC5AC as potential candidates for ADC development. Finally, we discuss current limits in using glycoepitope-targeting ADCs to treat cancer and propose methods to improve their efficacy and specificity.

antibody-drug conjugate
cancer treatment
PJT-166180/Canadian Institutes of Health Research
707343/Canadian Cancer Society Challenge Grant
Research Trainee Award from the Michael Smith Foundation for Health Research
Fig. 1.
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