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Development of a human antibody fragment directed against the alpha folate receptor as a promising molecule for targeted application
Alpha folate receptor (FRα) is currently under investigation as a target for the treatment of patients with non-small-cell lung cancer (NSCLC), since it is highly expressed in tumor cells but is largely absent in normal tissue. In this study, a novel human variable domain of a heavy-chain (VH) antib...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274507/ https://www.ncbi.nlm.nih.gov/pubmed/34236266 http://dx.doi.org/10.1080/10717544.2021.1943055 |
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author | Parakasikron, Nattihda Chaotham, Chatchai Chanvorachote, Pithi Vinayanuwattikun, Chanida Buranasudja, Visarut Taweecheep, Pornchanok Khantasup, Kannika |
author_facet | Parakasikron, Nattihda Chaotham, Chatchai Chanvorachote, Pithi Vinayanuwattikun, Chanida Buranasudja, Visarut Taweecheep, Pornchanok Khantasup, Kannika |
author_sort | Parakasikron, Nattihda |
collection | PubMed |
description | Alpha folate receptor (FRα) is currently under investigation as a target for the treatment of patients with non-small-cell lung cancer (NSCLC), since it is highly expressed in tumor cells but is largely absent in normal tissue. In this study, a novel human variable domain of a heavy-chain (VH) antibody fragment specific to FRα was enriched and selected by phage bio-planning. The positive phage clone (3A102 VH) specifically bound to FRα and also cross-reacted with FRβ, as tested by ELISA. Clone 3A102 VH was then successfully expressed as a soluble protein in an E. coli shuffle strain. The obtained soluble 3A102 VH demonstrated a high affinity for FRα with affinity constants (K(aff)) values around 7.77 ± 0.25 × 10(7) M(−1), with specific binding against both FRα expressing NSCLC cells and NSCLC patient-derived primary cancer cells, as tested by cell ELISA. In addition, soluble 3A102 VH showed the potential desired property of a targeting molecule by being internalized into FRα-expressing cells, as observed by confocal microscopy. This study inspires the use of phage display to develop human VH antibody (Ab) fragments that might be well suited for drug targeted therapy of NSCLC and other FRα-positive cancer cells. |
format | Online Article Text |
id | pubmed-8274507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-82745072021-07-20 Development of a human antibody fragment directed against the alpha folate receptor as a promising molecule for targeted application Parakasikron, Nattihda Chaotham, Chatchai Chanvorachote, Pithi Vinayanuwattikun, Chanida Buranasudja, Visarut Taweecheep, Pornchanok Khantasup, Kannika Drug Deliv Research Article Alpha folate receptor (FRα) is currently under investigation as a target for the treatment of patients with non-small-cell lung cancer (NSCLC), since it is highly expressed in tumor cells but is largely absent in normal tissue. In this study, a novel human variable domain of a heavy-chain (VH) antibody fragment specific to FRα was enriched and selected by phage bio-planning. The positive phage clone (3A102 VH) specifically bound to FRα and also cross-reacted with FRβ, as tested by ELISA. Clone 3A102 VH was then successfully expressed as a soluble protein in an E. coli shuffle strain. The obtained soluble 3A102 VH demonstrated a high affinity for FRα with affinity constants (K(aff)) values around 7.77 ± 0.25 × 10(7) M(−1), with specific binding against both FRα expressing NSCLC cells and NSCLC patient-derived primary cancer cells, as tested by cell ELISA. In addition, soluble 3A102 VH showed the potential desired property of a targeting molecule by being internalized into FRα-expressing cells, as observed by confocal microscopy. This study inspires the use of phage display to develop human VH antibody (Ab) fragments that might be well suited for drug targeted therapy of NSCLC and other FRα-positive cancer cells. Taylor & Francis 2021-07-08 /pmc/articles/PMC8274507/ /pubmed/34236266 http://dx.doi.org/10.1080/10717544.2021.1943055 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Parakasikron, Nattihda Chaotham, Chatchai Chanvorachote, Pithi Vinayanuwattikun, Chanida Buranasudja, Visarut Taweecheep, Pornchanok Khantasup, Kannika Development of a human antibody fragment directed against the alpha folate receptor as a promising molecule for targeted application |
title | Development of a human antibody fragment directed against the alpha folate receptor as a promising molecule for targeted application |
title_full | Development of a human antibody fragment directed against the alpha folate receptor as a promising molecule for targeted application |
title_fullStr | Development of a human antibody fragment directed against the alpha folate receptor as a promising molecule for targeted application |
title_full_unstemmed | Development of a human antibody fragment directed against the alpha folate receptor as a promising molecule for targeted application |
title_short | Development of a human antibody fragment directed against the alpha folate receptor as a promising molecule for targeted application |
title_sort | development of a human antibody fragment directed against the alpha folate receptor as a promising molecule for targeted application |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274507/ https://www.ncbi.nlm.nih.gov/pubmed/34236266 http://dx.doi.org/10.1080/10717544.2021.1943055 |
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