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Defucosylated Mouse–Dog Chimeric Anti-EGFR Antibody Exerts Antitumor Activities in Mouse Xenograft Models of Canine Tumors

The epidermal growth factor receptor (EGFR) contributes to tumor malignancy via gene amplification and protein overexpression. Previously, we developed an anti-human EGFR (hEGFR) monoclonal antibody, namely EMab-134, which detects hEGFR and dog EGFR (dEGFR) with high sensitivity and specificity. In...

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Autores principales: Li, Guanjie, Ohishi, Tomokazu, Kaneko, Mika K., Takei, Junko, Mizuno, Takuya, Kawada, Manabu, Saito, Masaki, Suzuki, Hiroyuki, Kato, Yukinari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700185/
https://www.ncbi.nlm.nih.gov/pubmed/34944112
http://dx.doi.org/10.3390/cells10123599
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author Li, Guanjie
Ohishi, Tomokazu
Kaneko, Mika K.
Takei, Junko
Mizuno, Takuya
Kawada, Manabu
Saito, Masaki
Suzuki, Hiroyuki
Kato, Yukinari
author_facet Li, Guanjie
Ohishi, Tomokazu
Kaneko, Mika K.
Takei, Junko
Mizuno, Takuya
Kawada, Manabu
Saito, Masaki
Suzuki, Hiroyuki
Kato, Yukinari
author_sort Li, Guanjie
collection PubMed
description The epidermal growth factor receptor (EGFR) contributes to tumor malignancy via gene amplification and protein overexpression. Previously, we developed an anti-human EGFR (hEGFR) monoclonal antibody, namely EMab-134, which detects hEGFR and dog EGFR (dEGFR) with high sensitivity and specificity. In this study, we produced a defucosylated mouse–dog chimeric anti-EGFR monoclonal antibody, namely E134Bf. In vitro analysis revealed that E134Bf highly exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against a canine osteosarcoma cell line (D-17) and a canine fibroblastic cell line (A-72), both of which express endogenous dEGFR. Moreover, in vivo administration of E134Bf significantly suppressed the development of D-17 and A-72 compared with the control dog IgG in mouse xenografts. These results indicate that E134Bf exerts antitumor effects against dEGFR-expressing canine cancers and could be valuable as part of an antibody treatment regimen for dogs.
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spelling pubmed-87001852021-12-24 Defucosylated Mouse–Dog Chimeric Anti-EGFR Antibody Exerts Antitumor Activities in Mouse Xenograft Models of Canine Tumors Li, Guanjie Ohishi, Tomokazu Kaneko, Mika K. Takei, Junko Mizuno, Takuya Kawada, Manabu Saito, Masaki Suzuki, Hiroyuki Kato, Yukinari Cells Article The epidermal growth factor receptor (EGFR) contributes to tumor malignancy via gene amplification and protein overexpression. Previously, we developed an anti-human EGFR (hEGFR) monoclonal antibody, namely EMab-134, which detects hEGFR and dog EGFR (dEGFR) with high sensitivity and specificity. In this study, we produced a defucosylated mouse–dog chimeric anti-EGFR monoclonal antibody, namely E134Bf. In vitro analysis revealed that E134Bf highly exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against a canine osteosarcoma cell line (D-17) and a canine fibroblastic cell line (A-72), both of which express endogenous dEGFR. Moreover, in vivo administration of E134Bf significantly suppressed the development of D-17 and A-72 compared with the control dog IgG in mouse xenografts. These results indicate that E134Bf exerts antitumor effects against dEGFR-expressing canine cancers and could be valuable as part of an antibody treatment regimen for dogs. MDPI 2021-12-20 /pmc/articles/PMC8700185/ /pubmed/34944112 http://dx.doi.org/10.3390/cells10123599 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Guanjie
Ohishi, Tomokazu
Kaneko, Mika K.
Takei, Junko
Mizuno, Takuya
Kawada, Manabu
Saito, Masaki
Suzuki, Hiroyuki
Kato, Yukinari
Defucosylated Mouse–Dog Chimeric Anti-EGFR Antibody Exerts Antitumor Activities in Mouse Xenograft Models of Canine Tumors
title Defucosylated Mouse–Dog Chimeric Anti-EGFR Antibody Exerts Antitumor Activities in Mouse Xenograft Models of Canine Tumors
title_full Defucosylated Mouse–Dog Chimeric Anti-EGFR Antibody Exerts Antitumor Activities in Mouse Xenograft Models of Canine Tumors
title_fullStr Defucosylated Mouse–Dog Chimeric Anti-EGFR Antibody Exerts Antitumor Activities in Mouse Xenograft Models of Canine Tumors
title_full_unstemmed Defucosylated Mouse–Dog Chimeric Anti-EGFR Antibody Exerts Antitumor Activities in Mouse Xenograft Models of Canine Tumors
title_short Defucosylated Mouse–Dog Chimeric Anti-EGFR Antibody Exerts Antitumor Activities in Mouse Xenograft Models of Canine Tumors
title_sort defucosylated mouse–dog chimeric anti-egfr antibody exerts antitumor activities in mouse xenograft models of canine tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700185/
https://www.ncbi.nlm.nih.gov/pubmed/34944112
http://dx.doi.org/10.3390/cells10123599
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