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Site-Specific Antibody–Drug Conjugates in Triple Variable Domain Fab Format
Open AccessArticle

Rapid Evaluation of Antibody Fragment Endocytosis for Antibody Fragment–Drug Conjugates

Department of Systems Immunology, Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Gangwon 24341, Korea
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine and College of Pharmacy, Seoul National University, Seoul 03080, Korea
Interdisciplinary Program in Cancer Biology Major, Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Korea
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Current address: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea.
Biomolecules 2020, 10(6), 955;
Received: 30 December 2019 / Revised: 12 June 2020 / Accepted: 23 June 2020 / Published: 25 June 2020
(This article belongs to the Special Issue Advances in Antibody Therapy of Cancer)
Antibody–drug conjugates (ADCs) have emerged as the most promising strategy in targeted cancer treatment. Recent strategies for the optimization ADCs include the development of antibody fragment–drug conjugates (FDCs). The critical factor in the successful development of ADCs and FDCs is the identification of tumor antigen-specific and internalizing antibodies (Abs). However, systematic comparison or correlation studies of internalization rates with different antibody formats have not been reported previously. In this study, we generated a panel of scFv-phage Abs using phage display technology and their corresponding scFv and scFv-Fc fragments and evaluated their relative internalization kinetics in relation to their antibody forms. We found that the relative rates and levels of internalization of scFv-phage antibodies positively correlate with their scFv and scFv-Fc forms. Our systematic study demonstrates that endocytosis of scFv-phage can serve as a predictive indicator for the assessment of Ab fragment internalization. Additionally, the present study demonstrates that endocytic antibodies can be rapidly screened and selected from phage antibody libraries prior to the conversion of phage antibodies for the generation of the conventional antibody format. Our strategic approach for the identification and evaluation of endocytic antibodies would expedite the selection for optimal antibodies and antibody fragments and be broadly applicable to ADC and FDC development. View Full-Text
Keywords: scFv-Fc; internalization; selection; cancer; antibody–drug conjugates; fragment–drug conjugates; scFv; phage display scFv-Fc; internalization; selection; cancer; antibody–drug conjugates; fragment–drug conjugates; scFv; phage display
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Kim, E.G.; Jeong, J.; Lee, J.; Jung, H.; Kim, M.; Zhao, Y.; Yi, E.C.; Kim, K.M. Rapid Evaluation of Antibody Fragment Endocytosis for Antibody Fragment–Drug Conjugates. Biomolecules 2020, 10, 955.

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