Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody 134-mG 2a -f Exerts Antitumor Activities in Mouse Xenograft Models of Dog Epidermal Growth Factor Receptor-Overexpressed Cells
The epidermal growth factor receptor (EGFR) is a type I transmembrane protein, which is a member of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. EGFR is a crucial mediator of cell growth and differentiation and forms homodimers or heterodimers with other HER...
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| Veröffentlicht in: | Monoclonal antibodies in immunodiagnosis and immunotherapy 2021-08, Vol.40 (4), p.177-183 |
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| creator | Tateyama, Nami Nanamiya, Ren Ohishi, Tomokazu Takei, Junko Nakamura, Takuro Yanaka, Miyuki Hosono, Hideki Saito, Masaki Asano, Teizo Tanaka, Tomohiro Sano, Masato Kawada, Manabu Kaneko, Mika K Kato, Yukinari |
| description | The epidermal growth factor receptor (EGFR) is a type I transmembrane protein, which is a member of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. EGFR is a crucial mediator of cell growth and differentiation and forms homodimers or heterodimers with other HER family members to activate downstream signaling cascades. We previously established an anti-human EGFR (hEGFR) monoclonal antibody (mAb), clone EMab-134 (mouse IgG
), by immunizing mice with the ectodomain of hEGFR. In this study, the subclass of EMab-134 was converted from IgG
to IgG
(134-mG
) and further defucosylated (134-mG
-f) to facilitate antibody-dependent cellular cytotoxicity (ADCC). Although 134-mG
-f was developed against hEGFR, it was shown to cross-react with dog EGFR (dEGFR) using flow cytometry. The dissociation constant (
) of 134-mG
-f against dEGFR-overexpressed CHO-K1 (CHO/dEGFR) cells was determined by flow cytometry to be 3.3 × 10
M, indicating that 134-mG
-f possesses a high binding affinity to dEGFR. Analysis
revealed that 134-mG
-f contributed to high levels of ADCC and complement-dependent cytotoxicity (CDC) in experiments targeting CHO/dEGFR cells. Furthermore, the
administration of 134-mG
-f significantly inhibited the development of CHO/dEGFR in comparison with the results observed in response to control mouse IgG. Taken together, the findings of this study demonstrate that 134-mG
-f could be useful as part of a therapeutic regimen for dEGFR-expressing canine cancers. |
| doi_str_mv | 10.1089/mab.2021.0022 |
| format | Article |
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), by immunizing mice with the ectodomain of hEGFR. In this study, the subclass of EMab-134 was converted from IgG
to IgG
(134-mG
) and further defucosylated (134-mG
-f) to facilitate antibody-dependent cellular cytotoxicity (ADCC). Although 134-mG
-f was developed against hEGFR, it was shown to cross-react with dog EGFR (dEGFR) using flow cytometry. The dissociation constant (
) of 134-mG
-f against dEGFR-overexpressed CHO-K1 (CHO/dEGFR) cells was determined by flow cytometry to be 3.3 × 10
M, indicating that 134-mG
-f possesses a high binding affinity to dEGFR. Analysis
revealed that 134-mG
-f contributed to high levels of ADCC and complement-dependent cytotoxicity (CDC) in experiments targeting CHO/dEGFR cells. Furthermore, the
administration of 134-mG
-f significantly inhibited the development of CHO/dEGFR in comparison with the results observed in response to control mouse IgG. Taken together, the findings of this study demonstrate that 134-mG
-f could be useful as part of a therapeutic regimen for dEGFR-expressing canine cancers.</description><identifier>ISSN: 2167-9436</identifier><identifier>EISSN: 2167-9436</identifier><identifier>DOI: 10.1089/mab.2021.0022</identifier><identifier>PMID: 34424762</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Antibodies, Monoclonal - pharmacology ; Cell Line, Tumor ; Cricetinae ; Dogs ; ErbB Receptors ; Heterografts ; Mice ; Xenograft Model Antitumor Assays</subject><ispartof>Monoclonal antibodies in immunodiagnosis and immunotherapy, 2021-08, Vol.40 (4), p.177-183</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1052-cbe86ff316cd5d56da5064ff35f2fcc8cd538f6553e7f6aa5141f13dba363bb43</citedby><cites>FETCH-LOGICAL-c1052-cbe86ff316cd5d56da5064ff35f2fcc8cd538f6553e7f6aa5141f13dba363bb43</cites><orcidid>0000-0001-5385-8201</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34424762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tateyama, Nami</creatorcontrib><creatorcontrib>Nanamiya, Ren</creatorcontrib><creatorcontrib>Ohishi, Tomokazu</creatorcontrib><creatorcontrib>Takei, Junko</creatorcontrib><creatorcontrib>Nakamura, Takuro</creatorcontrib><creatorcontrib>Yanaka, Miyuki</creatorcontrib><creatorcontrib>Hosono, Hideki</creatorcontrib><creatorcontrib>Saito, Masaki</creatorcontrib><creatorcontrib>Asano, Teizo</creatorcontrib><creatorcontrib>Tanaka, Tomohiro</creatorcontrib><creatorcontrib>Sano, Masato</creatorcontrib><creatorcontrib>Kawada, Manabu</creatorcontrib><creatorcontrib>Kaneko, Mika K</creatorcontrib><creatorcontrib>Kato, Yukinari</creatorcontrib><title>Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody 134-mG 2a -f Exerts Antitumor Activities in Mouse Xenograft Models of Dog Epidermal Growth Factor Receptor-Overexpressed Cells</title><title>Monoclonal antibodies in immunodiagnosis and immunotherapy</title><addtitle>Monoclon Antib Immunodiagn Immunother</addtitle><description>The epidermal growth factor receptor (EGFR) is a type I transmembrane protein, which is a member of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. EGFR is a crucial mediator of cell growth and differentiation and forms homodimers or heterodimers with other HER family members to activate downstream signaling cascades. We previously established an anti-human EGFR (hEGFR) monoclonal antibody (mAb), clone EMab-134 (mouse IgG
), by immunizing mice with the ectodomain of hEGFR. In this study, the subclass of EMab-134 was converted from IgG
to IgG
(134-mG
) and further defucosylated (134-mG
-f) to facilitate antibody-dependent cellular cytotoxicity (ADCC). Although 134-mG
-f was developed against hEGFR, it was shown to cross-react with dog EGFR (dEGFR) using flow cytometry. The dissociation constant (
) of 134-mG
-f against dEGFR-overexpressed CHO-K1 (CHO/dEGFR) cells was determined by flow cytometry to be 3.3 × 10
M, indicating that 134-mG
-f possesses a high binding affinity to dEGFR. Analysis
revealed that 134-mG
-f contributed to high levels of ADCC and complement-dependent cytotoxicity (CDC) in experiments targeting CHO/dEGFR cells. Furthermore, the
administration of 134-mG
-f significantly inhibited the development of CHO/dEGFR in comparison with the results observed in response to control mouse IgG. Taken together, the findings of this study demonstrate that 134-mG
-f could be useful as part of a therapeutic regimen for dEGFR-expressing canine cancers.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Cricetinae</subject><subject>Dogs</subject><subject>ErbB Receptors</subject><subject>Heterografts</subject><subject>Mice</subject><subject>Xenograft Model Antitumor Assays</subject><issn>2167-9436</issn><issn>2167-9436</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1KAzEUhYMoKtqlW8kLpOZnktZlqbUKFUEU3A2Z5EZHZiZDkmr7gj6XGf9wZzb35uScmwsfQieMjhmdnp-1uhpzytmYUs530CFnakLOC6F2__QHaBTjC81nwjgTch8diKLgxUTxQ_R-AW5tfNw2OoHFsy7VZNHXFkKrG7wM_i0940ttkg_4Dgz0Q3PjO28a32XHEKi83WImCtIuMdeYOLzYQEjx8zGt25yYmVS_1qmGiOsu59cR8CN0_ilol_LdQhOxd_jCP-H_vie3rxBg0weIMa88h6aJx2jP6SbC6LseoYfLxf38iqxul9fz2YoYRiUnpoKpck4wZay0UlktqSqyIB13xkyzKqZOSSlg4pTWkhXMMWErLZSoqkIcIfI11wQfYwBX9qFuddiWjJYDkjIjKQck5YAk-0-__P26asH-un8AiA8D44sD</recordid><startdate>202108</startdate><enddate>202108</enddate><creator>Tateyama, Nami</creator><creator>Nanamiya, Ren</creator><creator>Ohishi, Tomokazu</creator><creator>Takei, Junko</creator><creator>Nakamura, Takuro</creator><creator>Yanaka, Miyuki</creator><creator>Hosono, Hideki</creator><creator>Saito, Masaki</creator><creator>Asano, Teizo</creator><creator>Tanaka, Tomohiro</creator><creator>Sano, Masato</creator><creator>Kawada, Manabu</creator><creator>Kaneko, Mika K</creator><creator>Kato, Yukinari</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0001-5385-8201</orcidid></search><sort><creationdate>202108</creationdate><title>Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody 134-mG 2a -f Exerts Antitumor Activities in Mouse Xenograft Models of Dog Epidermal Growth Factor Receptor-Overexpressed Cells</title><author>Tateyama, Nami ; Nanamiya, Ren ; Ohishi, Tomokazu ; Takei, Junko ; Nakamura, Takuro ; Yanaka, Miyuki ; Hosono, Hideki ; Saito, Masaki ; Asano, Teizo ; Tanaka, Tomohiro ; Sano, Masato ; Kawada, Manabu ; Kaneko, Mika K ; Kato, Yukinari</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1052-cbe86ff316cd5d56da5064ff35f2fcc8cd538f6553e7f6aa5141f13dba363bb43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>Cricetinae</topic><topic>Dogs</topic><topic>ErbB Receptors</topic><topic>Heterografts</topic><topic>Mice</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tateyama, Nami</creatorcontrib><creatorcontrib>Nanamiya, Ren</creatorcontrib><creatorcontrib>Ohishi, Tomokazu</creatorcontrib><creatorcontrib>Takei, Junko</creatorcontrib><creatorcontrib>Nakamura, Takuro</creatorcontrib><creatorcontrib>Yanaka, Miyuki</creatorcontrib><creatorcontrib>Hosono, Hideki</creatorcontrib><creatorcontrib>Saito, Masaki</creatorcontrib><creatorcontrib>Asano, Teizo</creatorcontrib><creatorcontrib>Tanaka, Tomohiro</creatorcontrib><creatorcontrib>Sano, Masato</creatorcontrib><creatorcontrib>Kawada, Manabu</creatorcontrib><creatorcontrib>Kaneko, Mika K</creatorcontrib><creatorcontrib>Kato, Yukinari</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Monoclonal antibodies in immunodiagnosis and immunotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tateyama, Nami</au><au>Nanamiya, Ren</au><au>Ohishi, Tomokazu</au><au>Takei, Junko</au><au>Nakamura, Takuro</au><au>Yanaka, Miyuki</au><au>Hosono, Hideki</au><au>Saito, Masaki</au><au>Asano, Teizo</au><au>Tanaka, Tomohiro</au><au>Sano, Masato</au><au>Kawada, Manabu</au><au>Kaneko, Mika K</au><au>Kato, Yukinari</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody 134-mG 2a -f Exerts Antitumor Activities in Mouse Xenograft Models of Dog Epidermal Growth Factor Receptor-Overexpressed Cells</atitle><jtitle>Monoclonal antibodies in immunodiagnosis and immunotherapy</jtitle><addtitle>Monoclon Antib Immunodiagn Immunother</addtitle><date>2021-08</date><risdate>2021</risdate><volume>40</volume><issue>4</issue><spage>177</spage><epage>183</epage><pages>177-183</pages><issn>2167-9436</issn><eissn>2167-9436</eissn><abstract>The epidermal growth factor receptor (EGFR) is a type I transmembrane protein, which is a member of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. EGFR is a crucial mediator of cell growth and differentiation and forms homodimers or heterodimers with other HER family members to activate downstream signaling cascades. We previously established an anti-human EGFR (hEGFR) monoclonal antibody (mAb), clone EMab-134 (mouse IgG
), by immunizing mice with the ectodomain of hEGFR. In this study, the subclass of EMab-134 was converted from IgG
to IgG
(134-mG
) and further defucosylated (134-mG
-f) to facilitate antibody-dependent cellular cytotoxicity (ADCC). Although 134-mG
-f was developed against hEGFR, it was shown to cross-react with dog EGFR (dEGFR) using flow cytometry. The dissociation constant (
) of 134-mG
-f against dEGFR-overexpressed CHO-K1 (CHO/dEGFR) cells was determined by flow cytometry to be 3.3 × 10
M, indicating that 134-mG
-f possesses a high binding affinity to dEGFR. Analysis
revealed that 134-mG
-f contributed to high levels of ADCC and complement-dependent cytotoxicity (CDC) in experiments targeting CHO/dEGFR cells. Furthermore, the
administration of 134-mG
-f significantly inhibited the development of CHO/dEGFR in comparison with the results observed in response to control mouse IgG. Taken together, the findings of this study demonstrate that 134-mG
-f could be useful as part of a therapeutic regimen for dEGFR-expressing canine cancers.</abstract><cop>United States</cop><pmid>34424762</pmid><doi>10.1089/mab.2021.0022</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-5385-8201</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2167-9436 |
| ispartof | Monoclonal antibodies in immunodiagnosis and immunotherapy, 2021-08, Vol.40 (4), p.177-183 |
| issn | 2167-9436 2167-9436 |
| language | eng |
| recordid | cdi_crossref_primary_10_1089_mab_2021_0022 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Animals Antibodies, Monoclonal - pharmacology Cell Line, Tumor Cricetinae Dogs ErbB Receptors Heterografts Mice Xenograft Model Antitumor Assays |
| title | Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody 134-mG 2a -f Exerts Antitumor Activities in Mouse Xenograft Models of Dog Epidermal Growth Factor Receptor-Overexpressed Cells |
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