A novel anti-CEACAM5 monoclonal antibody, CC4, suppresses colorectal tumor growth and enhances NK cells-mediated tumor immunity
Carcinoembryonic antigen (CEA, CEACAM5, and CD66e) has been found to be associated with various types of cancers, particularly colorectal carcinoma, and developed to be a molecular target for cancer diagnosis and therapy. In present study, we generated a novel anti-CEACAM5 monoclonal antibody, namel...
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| Veröffentlicht in: | PloS one 2011-06, Vol.6 (6), p.e21146-e21146 |
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| creator | Zheng, Chaogu Feng, Jing Lu, Di Wang, Ping Xing, Shu Coll, Jean-Luc Yang, Dongling Yan, Xiyun |
| description | Carcinoembryonic antigen (CEA, CEACAM5, and CD66e) has been found to be associated with various types of cancers, particularly colorectal carcinoma, and developed to be a molecular target for cancer diagnosis and therapy. In present study, we generated a novel anti-CEACAM5 monoclonal antibody, namely mAb CC4, by immunizing mice with living colorectal cancer LS174T cells. Immunohistochemical studies found that mAb CC4 specifically and strongly binds to tumor tissues, especially colorectal adenocarcinoma. In xenografted mice, mAb CC4 is specifically accumulated in tumor site and remarkably represses colorectal tumor growth. In vitro functional analysis showed that mAb CC4 significantly suppresses cell proliferation, migration and aggregation of colorectal cancer cells and also raises strong ADCC reaction. More interestingly, mAb CC4 is able to enhance NK cytotoxicity against MHC-I-deficient colorectal cancer cells by blocking intercellular interaction between epithelial CEACAM5 and NK inhibitory receptor CEACAM1. These data suggest that mAb CC4 has the potential to be developed as a novel tumor-targeting carrier and cancer therapeutic. |
| doi_str_mv | 10.1371/journal.pone.0021146 |
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In present study, we generated a novel anti-CEACAM5 monoclonal antibody, namely mAb CC4, by immunizing mice with living colorectal cancer LS174T cells. Immunohistochemical studies found that mAb CC4 specifically and strongly binds to tumor tissues, especially colorectal adenocarcinoma. In xenografted mice, mAb CC4 is specifically accumulated in tumor site and remarkably represses colorectal tumor growth. In vitro functional analysis showed that mAb CC4 significantly suppresses cell proliferation, migration and aggregation of colorectal cancer cells and also raises strong ADCC reaction. More interestingly, mAb CC4 is able to enhance NK cytotoxicity against MHC-I-deficient colorectal cancer cells by blocking intercellular interaction between epithelial CEACAM5 and NK inhibitory receptor CEACAM1. These data suggest that mAb CC4 has the potential to be developed as a novel tumor-targeting carrier and cancer therapeutic.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0021146</identifier><identifier>PMID: 21731662</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Adhesives ; Amino Acid Sequence ; Animal tissues ; Animals ; Antibodies, Monoclonal - chemistry ; Antibodies, Monoclonal - immunology ; Antibody Specificity - immunology ; Antibody-Dependent Cell Cytotoxicity - immunology ; Antigens ; Antigens - immunology ; Biology ; Biophysics ; Cancer ; Cancer treatment ; Carcinoembryonic antigen ; Carcinoembryonic Antigen - immunology ; CD66 antigen ; CEACAM1 protein ; Cell adhesion & migration ; Cell Aggregation ; Cell Movement ; Cell Proliferation ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - immunology ; Colorectal Neoplasms - pathology ; Cytotoxicity ; Epitope Mapping ; Flow cytometry ; Functional analysis ; Gastrointestinal diseases ; Growth ; Health aspects ; House mouse ; Humans ; Immunity ; Immunity, Cellular - immunology ; Immunization ; Immunoglobulins ; Killer cells ; Killer Cells, Natural - cytology ; Killer Cells, Natural - immunology ; Laboratories ; Major histocompatibility complex ; Medicine ; Metastasis ; Mice ; Molecular Sequence Data ; Monoclonal antibodies ; Proteins ; Toxicity ; Tumors ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>PloS one, 2011-06, Vol.6 (6), p.e21146-e21146</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Zheng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Zheng et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-2b31025bb2e39fd54f6892dc91b025b433d16effbd59ea0a71d440190e610a7a3</citedby><cites>FETCH-LOGICAL-c691t-2b31025bb2e39fd54f6892dc91b025b433d16effbd59ea0a71d440190e610a7a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120848/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120848/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,2927,23865,27923,27924,53790,53792,79471,79472</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21731662$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zimmer, Jacques</contributor><creatorcontrib>Zheng, Chaogu</creatorcontrib><creatorcontrib>Feng, Jing</creatorcontrib><creatorcontrib>Lu, Di</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Xing, Shu</creatorcontrib><creatorcontrib>Coll, Jean-Luc</creatorcontrib><creatorcontrib>Yang, Dongling</creatorcontrib><creatorcontrib>Yan, Xiyun</creatorcontrib><title>A novel anti-CEACAM5 monoclonal antibody, CC4, suppresses colorectal tumor growth and enhances NK cells-mediated tumor immunity</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Carcinoembryonic antigen (CEA, CEACAM5, and CD66e) has been found to be associated with various types of cancers, particularly colorectal carcinoma, and developed to be a molecular target for cancer diagnosis and therapy. 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chemistry</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibody Specificity - immunology</topic><topic>Antibody-Dependent Cell Cytotoxicity - immunology</topic><topic>Antigens</topic><topic>Antigens - immunology</topic><topic>Biology</topic><topic>Biophysics</topic><topic>Cancer</topic><topic>Cancer treatment</topic><topic>Carcinoembryonic antigen</topic><topic>Carcinoembryonic Antigen - immunology</topic><topic>CD66 antigen</topic><topic>CEACAM1 protein</topic><topic>Cell adhesion & migration</topic><topic>Cell Aggregation</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - immunology</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Cytotoxicity</topic><topic>Epitope Mapping</topic><topic>Flow cytometry</topic><topic>Functional analysis</topic><topic>Gastrointestinal diseases</topic><topic>Growth</topic><topic>Health aspects</topic><topic>House mouse</topic><topic>Humans</topic><topic>Immunity</topic><topic>Immunity, Cellular - 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In present study, we generated a novel anti-CEACAM5 monoclonal antibody, namely mAb CC4, by immunizing mice with living colorectal cancer LS174T cells. Immunohistochemical studies found that mAb CC4 specifically and strongly binds to tumor tissues, especially colorectal adenocarcinoma. In xenografted mice, mAb CC4 is specifically accumulated in tumor site and remarkably represses colorectal tumor growth. In vitro functional analysis showed that mAb CC4 significantly suppresses cell proliferation, migration and aggregation of colorectal cancer cells and also raises strong ADCC reaction. More interestingly, mAb CC4 is able to enhance NK cytotoxicity against MHC-I-deficient colorectal cancer cells by blocking intercellular interaction between epithelial CEACAM5 and NK inhibitory receptor CEACAM1. These data suggest that mAb CC4 has the potential to be developed as a novel tumor-targeting carrier and cancer therapeutic.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21731662</pmid><doi>10.1371/journal.pone.0021146</doi><tpages>e21146</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenocarcinoma Adhesives Amino Acid Sequence Animal tissues Animals Antibodies, Monoclonal - chemistry Antibodies, Monoclonal - immunology Antibody Specificity - immunology Antibody-Dependent Cell Cytotoxicity - immunology Antigens Antigens - immunology Biology Biophysics Cancer Cancer treatment Carcinoembryonic antigen Carcinoembryonic Antigen - immunology CD66 antigen CEACAM1 protein Cell adhesion & migration Cell Aggregation Cell Movement Cell Proliferation Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - immunology Colorectal Neoplasms - pathology Cytotoxicity Epitope Mapping Flow cytometry Functional analysis Gastrointestinal diseases Growth Health aspects House mouse Humans Immunity Immunity, Cellular - immunology Immunization Immunoglobulins Killer cells Killer Cells, Natural - cytology Killer Cells, Natural - immunology Laboratories Major histocompatibility complex Medicine Metastasis Mice Molecular Sequence Data Monoclonal antibodies Proteins Toxicity Tumors Xenograft Model Antitumor Assays Xenografts |
| title | A novel anti-CEACAM5 monoclonal antibody, CC4, suppresses colorectal tumor growth and enhances NK cells-mediated tumor immunity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T08%3A56%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20novel%20anti-CEACAM5%20monoclonal%20antibody,%20CC4,%20suppresses%20colorectal%20tumor%20growth%20and%20enhances%20NK%20cells-mediated%20tumor%20immunity&rft.jtitle=PloS%20one&rft.au=Zheng,%20Chaogu&rft.date=2011-06-22&rft.volume=6&rft.issue=6&rft.spage=e21146&rft.epage=e21146&rft.pages=e21146-e21146&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0021146&rft_dat=%3Cgale_plos_%3EA476887677%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1305015059&rft_id=info:pmid/21731662&rft_galeid=A476887677&rft_doaj_id=oai_doaj_org_article_f470a044dc7b4305b9f30b2c55428f36&rfr_iscdi=true |