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

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 identif...

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Autores principales: Kim, Eunhee G., Jeong, Jieun, Lee, Junghyeon, Jung, Hyeryeon, Kim, Minho, Zhao, Yi, Yi, Eugene C., Kim, Kristine M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355425/
https://www.ncbi.nlm.nih.gov/pubmed/32630402
http://dx.doi.org/10.3390/biom10060955
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author Kim, Eunhee G.
Jeong, Jieun
Lee, Junghyeon
Jung, Hyeryeon
Kim, Minho
Zhao, Yi
Yi, Eugene C.
Kim, Kristine M.
author_facet Kim, Eunhee G.
Jeong, Jieun
Lee, Junghyeon
Jung, Hyeryeon
Kim, Minho
Zhao, Yi
Yi, Eugene C.
Kim, Kristine M.
author_sort Kim, Eunhee G.
collection PubMed
description 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.
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spelling pubmed-73554252020-07-23 Rapid Evaluation of Antibody Fragment Endocytosis for Antibody Fragment–Drug Conjugates Kim, Eunhee G. Jeong, Jieun Lee, Junghyeon Jung, Hyeryeon Kim, Minho Zhao, Yi Yi, Eugene C. Kim, Kristine M. Biomolecules Article 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. MDPI 2020-06-25 /pmc/articles/PMC7355425/ /pubmed/32630402 http://dx.doi.org/10.3390/biom10060955 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Eunhee G.
Jeong, Jieun
Lee, Junghyeon
Jung, Hyeryeon
Kim, Minho
Zhao, Yi
Yi, Eugene C.
Kim, Kristine M.
Rapid Evaluation of Antibody Fragment Endocytosis for Antibody Fragment–Drug Conjugates
title Rapid Evaluation of Antibody Fragment Endocytosis for Antibody Fragment–Drug Conjugates
title_full Rapid Evaluation of Antibody Fragment Endocytosis for Antibody Fragment–Drug Conjugates
title_fullStr Rapid Evaluation of Antibody Fragment Endocytosis for Antibody Fragment–Drug Conjugates
title_full_unstemmed Rapid Evaluation of Antibody Fragment Endocytosis for Antibody Fragment–Drug Conjugates
title_short Rapid Evaluation of Antibody Fragment Endocytosis for Antibody Fragment–Drug Conjugates
title_sort rapid evaluation of antibody fragment endocytosis for antibody fragment–drug conjugates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355425/
https://www.ncbi.nlm.nih.gov/pubmed/32630402
http://dx.doi.org/10.3390/biom10060955
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