Anti-HER2 antibody therapy using gene-transduced adipocytes for HER2-positive breast cancer
Purpose Although recent advances in molecular target therapy have improved the survival of breast cancer patients, high cost and frequent hospital visits result in both societal and individual burden. To reduce these problems, it has been proposed to produce antibodies in vivo. Here, we constructed...
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| Veröffentlicht in: | Breast cancer research and treatment 2020-04, Vol.180 (3), p.625-634 |
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| creator | Masuda, Takahito Fujimoto, Hiroshi Teranaka, Ryotaro Kuroda, Masayuki Aoyagi, Yasuyuki Nagashima, Takeshi Sangai, Takafumi Takada, Mamoru Nakagawa, Ayako Kubota, Yoshitaka Yokote, Koutaro Ohtsuka, Masayuki |
| description | Purpose
Although recent advances in molecular target therapy have improved the survival of breast cancer patients, high cost and frequent hospital visits result in both societal and individual burden. To reduce these problems, it has been proposed to produce antibodies in vivo. Here, we constructed gene-transduced human ceiling culture-derived proliferative adipocytes secreting anti-HER2 antibody (HER2-ccdPAs) and evaluated their ability to secrete antibody and mediate an anti-tumor effect.
Methods
Plasmid lentivirus was used as a recipient for anti-HER2 antibody cDNA and transduced into human proliferative adipocyte. Secretory antibody expression was evaluated by ELISA and western blot. Specific binding of secretory antibody to HER2 was examined by immunofluorescence analysis. Direct and indirect anti-tumor effects of supernatants from HER2-ccdPAs were evaluated using BT474 (HER2+) and MDA-MB-231 (HER2−) breast cancer cell lines. Additionally, whether adipocyte differentiation affects antibody secretion was investigated using supernatant collected from different cell maturation states.
Results
Anti-HER2 antibody was identified in the supernatant from HER2-ccdPAs and its production increased with the differentiation into mature adipocyte. Antibodies in supernatants from HER2-ccdPAs bound to HER2-positive breast cancer cells similar to trastuzumab. Supernatant from HER2-ccdPAs inhibited the proliferation of BT474 but not MDA-MB-231 cells, and downregulated AKT phosphorylation in BT474 cells compared with controls. Supernatants from HER2-ccdPAs also had an indirect anti-tumor effect on BT474 cells through ADCC. Additionally, Single inoculation of HER2-ccdPAs showed an anti-tumor effect in BT474 xenograft model.
Conclusions
HER2-ccdPAs might be useful for cell-based gene therapy. This system could be a platform for various antibody therapies. |
| doi_str_mv | 10.1007/s10549-020-05581-x |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2370532030</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A618892077</galeid><sourcerecordid>A618892077</sourcerecordid><originalsourceid>FETCH-LOGICAL-c539t-eb0f166500a972db4089799045c302cf6669d95e9d89f33e6eaae31cfe1db9453</originalsourceid><addsrcrecordid>eNp9kVFrFDEUhQdR7Fr9Az7IgCC-pN4kk2TyuJRqhYIg-uRDyGTu7KbMJmMyU7r_3qxbrRWRPCQk3znck1NVLymcUQD1LlMQjSbAgIAQLSW3j6oVFYoTxah6XK2ASkVkC_KkepbzNQBoBfppdcIZZQ3lYlV9W4fZk8uLz6y25dTFfl_PW0x22tdL9mFTbzAgmZMNuV8c9rXt_RTdfsZcDzHVBymZYvazv8G6S2jzXDsbHKbn1ZPBjhlf3O2n1df3F1_OL8nVpw8fz9dXxAmuZ4IdDFRKAWC1Yn3XQKuV1tAIx4G5QUqpey1Q960eOEeJ1iKnbkDad7oR_LR6e_SdUvy-YJ7NzmeH42gDxiUbxhUIzoBDQV__hV7HJYUyXaFa3qryWfSe2tgRjQ9DLPndwdSsJW1bzUCpQp39gyqrx513MeDgy_0DwZs_BFu047zNcVxmH0N-CLIj6FLMOeFgpuR3Nu0NBXOo3hyrN6V687N6c1tEr-6iLd0O-9-SX10XgB-BXJ7CBtN99v_Y_gAH4bZz</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2383878061</pqid></control><display><type>article</type><title>Anti-HER2 antibody therapy using gene-transduced adipocytes for HER2-positive breast cancer</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Masuda, Takahito ; Fujimoto, Hiroshi ; Teranaka, Ryotaro ; Kuroda, Masayuki ; Aoyagi, Yasuyuki ; Nagashima, Takeshi ; Sangai, Takafumi ; Takada, Mamoru ; Nakagawa, Ayako ; Kubota, Yoshitaka ; Yokote, Koutaro ; Ohtsuka, Masayuki</creator><creatorcontrib>Masuda, Takahito ; Fujimoto, Hiroshi ; Teranaka, Ryotaro ; Kuroda, Masayuki ; Aoyagi, Yasuyuki ; Nagashima, Takeshi ; Sangai, Takafumi ; Takada, Mamoru ; Nakagawa, Ayako ; Kubota, Yoshitaka ; Yokote, Koutaro ; Ohtsuka, Masayuki</creatorcontrib><description>Purpose
Although recent advances in molecular target therapy have improved the survival of breast cancer patients, high cost and frequent hospital visits result in both societal and individual burden. To reduce these problems, it has been proposed to produce antibodies in vivo. Here, we constructed gene-transduced human ceiling culture-derived proliferative adipocytes secreting anti-HER2 antibody (HER2-ccdPAs) and evaluated their ability to secrete antibody and mediate an anti-tumor effect.
Methods
Plasmid lentivirus was used as a recipient for anti-HER2 antibody cDNA and transduced into human proliferative adipocyte. Secretory antibody expression was evaluated by ELISA and western blot. Specific binding of secretory antibody to HER2 was examined by immunofluorescence analysis. Direct and indirect anti-tumor effects of supernatants from HER2-ccdPAs were evaluated using BT474 (HER2+) and MDA-MB-231 (HER2−) breast cancer cell lines. Additionally, whether adipocyte differentiation affects antibody secretion was investigated using supernatant collected from different cell maturation states.
Results
Anti-HER2 antibody was identified in the supernatant from HER2-ccdPAs and its production increased with the differentiation into mature adipocyte. Antibodies in supernatants from HER2-ccdPAs bound to HER2-positive breast cancer cells similar to trastuzumab. Supernatant from HER2-ccdPAs inhibited the proliferation of BT474 but not MDA-MB-231 cells, and downregulated AKT phosphorylation in BT474 cells compared with controls. Supernatants from HER2-ccdPAs also had an indirect anti-tumor effect on BT474 cells through ADCC. Additionally, Single inoculation of HER2-ccdPAs showed an anti-tumor effect in BT474 xenograft model.
Conclusions
HER2-ccdPAs might be useful for cell-based gene therapy. This system could be a platform for various antibody therapies.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-020-05581-x</identifier><identifier>PMID: 32124135</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adipocytes ; Adipocytes - cytology ; Adipocytes - metabolism ; AKT protein ; Analysis ; Animals ; Antibodies ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - metabolism ; Apoptosis ; Biopharmaceutics ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - immunology ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cancer ; Cancer research ; Care and treatment ; Cell culture ; Cell Differentiation ; Cell Movement ; Cell Proliferation ; Enzyme-linked immunosorbent assay ; ErbB-2 protein ; Female ; Gene therapy ; Genes ; Genetic aspects ; Humans ; Immunofluorescence ; Immunotherapy ; Inoculation ; Medical care, Cost of ; Medical colleges ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Monoclonal antibodies ; Neomycin ; Oncology ; Phosphorylation ; Preclinical Study ; Receptor, ErbB-2 - antagonists & inhibitors ; Receptor, ErbB-2 - immunology ; Targeted cancer therapy ; Trastuzumab ; Tumor cell lines ; Tumor Cells, Cultured ; Viral antibodies ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>Breast cancer research and treatment, 2020-04, Vol.180 (3), p.625-634</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>COPYRIGHT 2020 Springer</rights><rights>Breast Cancer Research and Treatment is a copyright of Springer, (2020). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-eb0f166500a972db4089799045c302cf6669d95e9d89f33e6eaae31cfe1db9453</citedby><cites>FETCH-LOGICAL-c539t-eb0f166500a972db4089799045c302cf6669d95e9d89f33e6eaae31cfe1db9453</cites><orcidid>0000-0002-4987-0715</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-020-05581-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-020-05581-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32124135$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Masuda, Takahito</creatorcontrib><creatorcontrib>Fujimoto, Hiroshi</creatorcontrib><creatorcontrib>Teranaka, Ryotaro</creatorcontrib><creatorcontrib>Kuroda, Masayuki</creatorcontrib><creatorcontrib>Aoyagi, Yasuyuki</creatorcontrib><creatorcontrib>Nagashima, Takeshi</creatorcontrib><creatorcontrib>Sangai, Takafumi</creatorcontrib><creatorcontrib>Takada, Mamoru</creatorcontrib><creatorcontrib>Nakagawa, Ayako</creatorcontrib><creatorcontrib>Kubota, Yoshitaka</creatorcontrib><creatorcontrib>Yokote, Koutaro</creatorcontrib><creatorcontrib>Ohtsuka, Masayuki</creatorcontrib><title>Anti-HER2 antibody therapy using gene-transduced adipocytes for HER2-positive breast cancer</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>Purpose
Although recent advances in molecular target therapy have improved the survival of breast cancer patients, high cost and frequent hospital visits result in both societal and individual burden. To reduce these problems, it has been proposed to produce antibodies in vivo. Here, we constructed gene-transduced human ceiling culture-derived proliferative adipocytes secreting anti-HER2 antibody (HER2-ccdPAs) and evaluated their ability to secrete antibody and mediate an anti-tumor effect.
Methods
Plasmid lentivirus was used as a recipient for anti-HER2 antibody cDNA and transduced into human proliferative adipocyte. Secretory antibody expression was evaluated by ELISA and western blot. Specific binding of secretory antibody to HER2 was examined by immunofluorescence analysis. Direct and indirect anti-tumor effects of supernatants from HER2-ccdPAs were evaluated using BT474 (HER2+) and MDA-MB-231 (HER2−) breast cancer cell lines. Additionally, whether adipocyte differentiation affects antibody secretion was investigated using supernatant collected from different cell maturation states.
Results
Anti-HER2 antibody was identified in the supernatant from HER2-ccdPAs and its production increased with the differentiation into mature adipocyte. Antibodies in supernatants from HER2-ccdPAs bound to HER2-positive breast cancer cells similar to trastuzumab. Supernatant from HER2-ccdPAs inhibited the proliferation of BT474 but not MDA-MB-231 cells, and downregulated AKT phosphorylation in BT474 cells compared with controls. Supernatants from HER2-ccdPAs also had an indirect anti-tumor effect on BT474 cells through ADCC. Additionally, Single inoculation of HER2-ccdPAs showed an anti-tumor effect in BT474 xenograft model.
Conclusions
HER2-ccdPAs might be useful for cell-based gene therapy. This system could be a platform for various antibody therapies.</description><subject>Adipocytes</subject><subject>Adipocytes - cytology</subject><subject>Adipocytes - metabolism</subject><subject>AKT protein</subject><subject>Analysis</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - metabolism</subject><subject>Apoptosis</subject><subject>Biopharmaceutics</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - immunology</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Cancer research</subject><subject>Care and treatment</subject><subject>Cell culture</subject><subject>Cell Differentiation</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>ErbB-2 protein</subject><subject>Female</subject><subject>Gene therapy</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Immunotherapy</subject><subject>Inoculation</subject><subject>Medical care, Cost of</subject><subject>Medical colleges</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Monoclonal antibodies</subject><subject>Neomycin</subject><subject>Oncology</subject><subject>Phosphorylation</subject><subject>Preclinical Study</subject><subject>Receptor, ErbB-2 - antagonists & inhibitors</subject><subject>Receptor, ErbB-2 - immunology</subject><subject>Targeted cancer therapy</subject><subject>Trastuzumab</subject><subject>Tumor cell lines</subject><subject>Tumor Cells, Cultured</subject><subject>Viral antibodies</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kVFrFDEUhQdR7Fr9Az7IgCC-pN4kk2TyuJRqhYIg-uRDyGTu7KbMJmMyU7r_3qxbrRWRPCQk3znck1NVLymcUQD1LlMQjSbAgIAQLSW3j6oVFYoTxah6XK2ASkVkC_KkepbzNQBoBfppdcIZZQ3lYlV9W4fZk8uLz6y25dTFfl_PW0x22tdL9mFTbzAgmZMNuV8c9rXt_RTdfsZcDzHVBymZYvazv8G6S2jzXDsbHKbn1ZPBjhlf3O2n1df3F1_OL8nVpw8fz9dXxAmuZ4IdDFRKAWC1Yn3XQKuV1tAIx4G5QUqpey1Q960eOEeJ1iKnbkDad7oR_LR6e_SdUvy-YJ7NzmeH42gDxiUbxhUIzoBDQV__hV7HJYUyXaFa3qryWfSe2tgRjQ9DLPndwdSsJW1bzUCpQp39gyqrx513MeDgy_0DwZs_BFu047zNcVxmH0N-CLIj6FLMOeFgpuR3Nu0NBXOo3hyrN6V687N6c1tEr-6iLd0O-9-SX10XgB-BXJ7CBtN99v_Y_gAH4bZz</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Masuda, Takahito</creator><creator>Fujimoto, Hiroshi</creator><creator>Teranaka, Ryotaro</creator><creator>Kuroda, Masayuki</creator><creator>Aoyagi, Yasuyuki</creator><creator>Nagashima, Takeshi</creator><creator>Sangai, Takafumi</creator><creator>Takada, Mamoru</creator><creator>Nakagawa, Ayako</creator><creator>Kubota, Yoshitaka</creator><creator>Yokote, Koutaro</creator><creator>Ohtsuka, Masayuki</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4987-0715</orcidid></search><sort><creationdate>20200401</creationdate><title>Anti-HER2 antibody therapy using gene-transduced adipocytes for HER2-positive breast cancer</title><author>Masuda, Takahito ; Fujimoto, Hiroshi ; Teranaka, Ryotaro ; Kuroda, Masayuki ; Aoyagi, Yasuyuki ; Nagashima, Takeshi ; Sangai, Takafumi ; Takada, Mamoru ; Nakagawa, Ayako ; Kubota, Yoshitaka ; Yokote, Koutaro ; Ohtsuka, Masayuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-eb0f166500a972db4089799045c302cf6669d95e9d89f33e6eaae31cfe1db9453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adipocytes</topic><topic>Adipocytes - cytology</topic><topic>Adipocytes - metabolism</topic><topic>AKT protein</topic><topic>Analysis</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - metabolism</topic><topic>Apoptosis</topic><topic>Biopharmaceutics</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - immunology</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer</topic><topic>Cancer research</topic><topic>Care and treatment</topic><topic>Cell culture</topic><topic>Cell Differentiation</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>ErbB-2 protein</topic><topic>Female</topic><topic>Gene therapy</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Humans</topic><topic>Immunofluorescence</topic><topic>Immunotherapy</topic><topic>Inoculation</topic><topic>Medical care, Cost of</topic><topic>Medical colleges</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Monoclonal antibodies</topic><topic>Neomycin</topic><topic>Oncology</topic><topic>Phosphorylation</topic><topic>Preclinical Study</topic><topic>Receptor, ErbB-2 - antagonists & inhibitors</topic><topic>Receptor, ErbB-2 - immunology</topic><topic>Targeted cancer therapy</topic><topic>Trastuzumab</topic><topic>Tumor cell lines</topic><topic>Tumor Cells, Cultured</topic><topic>Viral antibodies</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Masuda, Takahito</creatorcontrib><creatorcontrib>Fujimoto, Hiroshi</creatorcontrib><creatorcontrib>Teranaka, Ryotaro</creatorcontrib><creatorcontrib>Kuroda, Masayuki</creatorcontrib><creatorcontrib>Aoyagi, Yasuyuki</creatorcontrib><creatorcontrib>Nagashima, Takeshi</creatorcontrib><creatorcontrib>Sangai, Takafumi</creatorcontrib><creatorcontrib>Takada, Mamoru</creatorcontrib><creatorcontrib>Nakagawa, Ayako</creatorcontrib><creatorcontrib>Kubota, Yoshitaka</creatorcontrib><creatorcontrib>Yokote, Koutaro</creatorcontrib><creatorcontrib>Ohtsuka, Masayuki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Masuda, Takahito</au><au>Fujimoto, Hiroshi</au><au>Teranaka, Ryotaro</au><au>Kuroda, Masayuki</au><au>Aoyagi, Yasuyuki</au><au>Nagashima, Takeshi</au><au>Sangai, Takafumi</au><au>Takada, Mamoru</au><au>Nakagawa, Ayako</au><au>Kubota, Yoshitaka</au><au>Yokote, Koutaro</au><au>Ohtsuka, Masayuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-HER2 antibody therapy using gene-transduced adipocytes for HER2-positive breast cancer</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>180</volume><issue>3</issue><spage>625</spage><epage>634</epage><pages>625-634</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><abstract>Purpose
Although recent advances in molecular target therapy have improved the survival of breast cancer patients, high cost and frequent hospital visits result in both societal and individual burden. To reduce these problems, it has been proposed to produce antibodies in vivo. Here, we constructed gene-transduced human ceiling culture-derived proliferative adipocytes secreting anti-HER2 antibody (HER2-ccdPAs) and evaluated their ability to secrete antibody and mediate an anti-tumor effect.
Methods
Plasmid lentivirus was used as a recipient for anti-HER2 antibody cDNA and transduced into human proliferative adipocyte. Secretory antibody expression was evaluated by ELISA and western blot. Specific binding of secretory antibody to HER2 was examined by immunofluorescence analysis. Direct and indirect anti-tumor effects of supernatants from HER2-ccdPAs were evaluated using BT474 (HER2+) and MDA-MB-231 (HER2−) breast cancer cell lines. Additionally, whether adipocyte differentiation affects antibody secretion was investigated using supernatant collected from different cell maturation states.
Results
Anti-HER2 antibody was identified in the supernatant from HER2-ccdPAs and its production increased with the differentiation into mature adipocyte. Antibodies in supernatants from HER2-ccdPAs bound to HER2-positive breast cancer cells similar to trastuzumab. Supernatant from HER2-ccdPAs inhibited the proliferation of BT474 but not MDA-MB-231 cells, and downregulated AKT phosphorylation in BT474 cells compared with controls. Supernatants from HER2-ccdPAs also had an indirect anti-tumor effect on BT474 cells through ADCC. Additionally, Single inoculation of HER2-ccdPAs showed an anti-tumor effect in BT474 xenograft model.
Conclusions
HER2-ccdPAs might be useful for cell-based gene therapy. This system could be a platform for various antibody therapies.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>32124135</pmid><doi>10.1007/s10549-020-05581-x</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-4987-0715</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-6806 |
| ispartof | Breast cancer research and treatment, 2020-04, Vol.180 (3), p.625-634 |
| issn | 0167-6806 1573-7217 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2370532030 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adipocytes Adipocytes - cytology Adipocytes - metabolism AKT protein Analysis Animals Antibodies Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - metabolism Apoptosis Biopharmaceutics Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - immunology Breast Neoplasms - metabolism Breast Neoplasms - pathology Cancer Cancer research Care and treatment Cell culture Cell Differentiation Cell Movement Cell Proliferation Enzyme-linked immunosorbent assay ErbB-2 protein Female Gene therapy Genes Genetic aspects Humans Immunofluorescence Immunotherapy Inoculation Medical care, Cost of Medical colleges Medicine Medicine & Public Health Mice Mice, Inbred BALB C Mice, Nude Monoclonal antibodies Neomycin Oncology Phosphorylation Preclinical Study Receptor, ErbB-2 - antagonists & inhibitors Receptor, ErbB-2 - immunology Targeted cancer therapy Trastuzumab Tumor cell lines Tumor Cells, Cultured Viral antibodies Xenograft Model Antitumor Assays Xenografts |
| title | Anti-HER2 antibody therapy using gene-transduced adipocytes for HER2-positive breast cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-19T15%3A21%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Anti-HER2%20antibody%20therapy%20using%20gene-transduced%20adipocytes%20for%20HER2-positive%20breast%20cancer&rft.jtitle=Breast%20cancer%20research%20and%20treatment&rft.au=Masuda,%20Takahito&rft.date=2020-04-01&rft.volume=180&rft.issue=3&rft.spage=625&rft.epage=634&rft.pages=625-634&rft.issn=0167-6806&rft.eissn=1573-7217&rft_id=info:doi/10.1007/s10549-020-05581-x&rft_dat=%3Cgale_proqu%3EA618892077%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2383878061&rft_id=info:pmid/32124135&rft_galeid=A618892077&rfr_iscdi=true |