Significant Impact of Immunogen Design on the Diversity of Antibodies Generated by Carbohydrate-Based Anticancer Vaccine

Development of an effective vaccine targeting tumor associated carbohydrate antigens (TACAs) is an appealing approach toward tumor immunotherapy. While much emphasis has been typically placed on generating high antibody titers against the immunizing antigen, the impact of immunogen design on the div...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:ACS chemical biology 2015-10, Vol.10 (10), p.2364-2372
Hauptverfasser: Yin, Zhaojun, Chowdhury, Sudipa, McKay, Craig, Baniel, Claire, Wright, W. Shea, Bentley, Philip, Kaczanowska, Katarzyna, Gildersleeve, Jeffrey C, Finn, M.G, BenMohamed, Lbachir, Huang, Xuefei
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 2372
container_issue 10
container_start_page 2364
container_title ACS chemical biology
container_volume 10
creator Yin, Zhaojun
Chowdhury, Sudipa
McKay, Craig
Baniel, Claire
Wright, W. Shea
Bentley, Philip
Kaczanowska, Katarzyna
Gildersleeve, Jeffrey C
Finn, M.G
BenMohamed, Lbachir
Huang, Xuefei
description Development of an effective vaccine targeting tumor associated carbohydrate antigens (TACAs) is an appealing approach toward tumor immunotherapy. While much emphasis has been typically placed on generating high antibody titers against the immunizing antigen, the impact of immunogen design on the diversity of TACA-specific antibodies elicited has been overlooked. Herein, we report that the immunogen structure can significantly impact the breadth and the magnitude of humoral responses. Vaccine constructs that induced diverse TACA-binding antibodies provided much stronger recognition of a variety of Tn positive tumor cells. Optimization of the breadth of the antibody response led to a vaccine construct that demonstrated long lasting efficacy in a mouse tumor model. After challenged with the highly aggressive TA3Ha cells, mice immunized with the new construct exhibited a statistically significant improvement in survival relative to controls (0% vs 50% survival; p < 0.0001). Furthermore, the surviving mice developed long-term immunity against TA3Ha. Thus, both the magnitude and the breadth of antibody reactivity should be considered when designing TACA-based antitumor vaccines.
doi_str_mv 10.1021/acschembio.5b00406
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4725323</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1722928428</sourcerecordid><originalsourceid>FETCH-LOGICAL-a441t-95f4924b338b25745e8b1eebbda71f6c4454543d70f0ca5641cbb5bf9a3c2d773</originalsourceid><addsrcrecordid>eNp9kU1rGzEQhkVJqFO3f6CHoGMu666-9uMSSJ2PBgI5pO1VSNpZW8YruZI2xP8-Mnbd5hLmoGH0zDvDvAh9JeWMlJR8UyaaJQza-pnQZcnL6gM6I0LwomlZfXLMaTtBn2JcZYRVTfsRTWiVo2HtGXp5sgtne2uUS_h-2CiTsO9zNozOL8Dha4iZwN7htAR8bZ8hRJu2O-jKJat9ZyHiO3AQVIIO6y2eq6D9ctvtCsV3FXN1h-YRBgL-rYyxDj6j016tI3w5vFP06_bm5_xH8fB4dz-_eigU5yQVreh5S7lmrNFU1FxAowmA1p2qSV8ZzkUO1tVlXxolKk6M1kL3rWKGdnXNpuhyr7sZ9QCdAZeCWstNsIMKW-mVlW9_nF3KhX-WvKaCUZYFLg4Cwf8ZISY52GhgvVYO_BglqSltacPzPaeI7lETfIwB-uMYUsqdZfKfZfJgWW46_3_BY8tfjzIw2wO5Wa78GFy-13uKr3Ewp20</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1722928428</pqid></control><display><type>article</type><title>Significant Impact of Immunogen Design on the Diversity of Antibodies Generated by Carbohydrate-Based Anticancer Vaccine</title><source>American Chemical Society</source><source>MEDLINE</source><creator>Yin, Zhaojun ; Chowdhury, Sudipa ; McKay, Craig ; Baniel, Claire ; Wright, W. Shea ; Bentley, Philip ; Kaczanowska, Katarzyna ; Gildersleeve, Jeffrey C ; Finn, M.G ; BenMohamed, Lbachir ; Huang, Xuefei</creator><creatorcontrib>Yin, Zhaojun ; Chowdhury, Sudipa ; McKay, Craig ; Baniel, Claire ; Wright, W. Shea ; Bentley, Philip ; Kaczanowska, Katarzyna ; Gildersleeve, Jeffrey C ; Finn, M.G ; BenMohamed, Lbachir ; Huang, Xuefei</creatorcontrib><description>Development of an effective vaccine targeting tumor associated carbohydrate antigens (TACAs) is an appealing approach toward tumor immunotherapy. While much emphasis has been typically placed on generating high antibody titers against the immunizing antigen, the impact of immunogen design on the diversity of TACA-specific antibodies elicited has been overlooked. Herein, we report that the immunogen structure can significantly impact the breadth and the magnitude of humoral responses. Vaccine constructs that induced diverse TACA-binding antibodies provided much stronger recognition of a variety of Tn positive tumor cells. Optimization of the breadth of the antibody response led to a vaccine construct that demonstrated long lasting efficacy in a mouse tumor model. After challenged with the highly aggressive TA3Ha cells, mice immunized with the new construct exhibited a statistically significant improvement in survival relative to controls (0% vs 50% survival; p &lt; 0.0001). Furthermore, the surviving mice developed long-term immunity against TA3Ha. Thus, both the magnitude and the breadth of antibody reactivity should be considered when designing TACA-based antitumor vaccines.</description><identifier>ISSN: 1554-8929</identifier><identifier>EISSN: 1554-8937</identifier><identifier>DOI: 10.1021/acschembio.5b00406</identifier><identifier>PMID: 26262839</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Antibodies - blood ; Antibodies - classification ; Antigens, Tumor-Associated, Carbohydrate - immunology ; Cancer Vaccines - chemistry ; Cancer Vaccines - immunology ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Immunotherapy ; Mice ; Mice, Inbred C57BL</subject><ispartof>ACS chemical biology, 2015-10, Vol.10 (10), p.2364-2372</ispartof><rights>Copyright © 2015 American Chemical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a441t-95f4924b338b25745e8b1eebbda71f6c4454543d70f0ca5641cbb5bf9a3c2d773</citedby><cites>FETCH-LOGICAL-a441t-95f4924b338b25745e8b1eebbda71f6c4454543d70f0ca5641cbb5bf9a3c2d773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acschembio.5b00406$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acschembio.5b00406$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,780,784,885,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26262839$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yin, Zhaojun</creatorcontrib><creatorcontrib>Chowdhury, Sudipa</creatorcontrib><creatorcontrib>McKay, Craig</creatorcontrib><creatorcontrib>Baniel, Claire</creatorcontrib><creatorcontrib>Wright, W. Shea</creatorcontrib><creatorcontrib>Bentley, Philip</creatorcontrib><creatorcontrib>Kaczanowska, Katarzyna</creatorcontrib><creatorcontrib>Gildersleeve, Jeffrey C</creatorcontrib><creatorcontrib>Finn, M.G</creatorcontrib><creatorcontrib>BenMohamed, Lbachir</creatorcontrib><creatorcontrib>Huang, Xuefei</creatorcontrib><title>Significant Impact of Immunogen Design on the Diversity of Antibodies Generated by Carbohydrate-Based Anticancer Vaccine</title><title>ACS chemical biology</title><addtitle>ACS Chem. Biol</addtitle><description>Development of an effective vaccine targeting tumor associated carbohydrate antigens (TACAs) is an appealing approach toward tumor immunotherapy. While much emphasis has been typically placed on generating high antibody titers against the immunizing antigen, the impact of immunogen design on the diversity of TACA-specific antibodies elicited has been overlooked. Herein, we report that the immunogen structure can significantly impact the breadth and the magnitude of humoral responses. Vaccine constructs that induced diverse TACA-binding antibodies provided much stronger recognition of a variety of Tn positive tumor cells. Optimization of the breadth of the antibody response led to a vaccine construct that demonstrated long lasting efficacy in a mouse tumor model. After challenged with the highly aggressive TA3Ha cells, mice immunized with the new construct exhibited a statistically significant improvement in survival relative to controls (0% vs 50% survival; p &lt; 0.0001). Furthermore, the surviving mice developed long-term immunity against TA3Ha. Thus, both the magnitude and the breadth of antibody reactivity should be considered when designing TACA-based antitumor vaccines.</description><subject>Animals</subject><subject>Antibodies - blood</subject><subject>Antibodies - classification</subject><subject>Antigens, Tumor-Associated, Carbohydrate - immunology</subject><subject>Cancer Vaccines - chemistry</subject><subject>Cancer Vaccines - immunology</subject><subject>Disease Models, Animal</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Immunotherapy</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><issn>1554-8929</issn><issn>1554-8937</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1rGzEQhkVJqFO3f6CHoGMu666-9uMSSJ2PBgI5pO1VSNpZW8YruZI2xP8-Mnbd5hLmoGH0zDvDvAh9JeWMlJR8UyaaJQza-pnQZcnL6gM6I0LwomlZfXLMaTtBn2JcZYRVTfsRTWiVo2HtGXp5sgtne2uUS_h-2CiTsO9zNozOL8Dha4iZwN7htAR8bZ8hRJu2O-jKJat9ZyHiO3AQVIIO6y2eq6D9ctvtCsV3FXN1h-YRBgL-rYyxDj6j016tI3w5vFP06_bm5_xH8fB4dz-_eigU5yQVreh5S7lmrNFU1FxAowmA1p2qSV8ZzkUO1tVlXxolKk6M1kL3rWKGdnXNpuhyr7sZ9QCdAZeCWstNsIMKW-mVlW9_nF3KhX-WvKaCUZYFLg4Cwf8ZISY52GhgvVYO_BglqSltacPzPaeI7lETfIwB-uMYUsqdZfKfZfJgWW46_3_BY8tfjzIw2wO5Wa78GFy-13uKr3Ewp20</recordid><startdate>20151016</startdate><enddate>20151016</enddate><creator>Yin, Zhaojun</creator><creator>Chowdhury, Sudipa</creator><creator>McKay, Craig</creator><creator>Baniel, Claire</creator><creator>Wright, W. Shea</creator><creator>Bentley, Philip</creator><creator>Kaczanowska, Katarzyna</creator><creator>Gildersleeve, Jeffrey C</creator><creator>Finn, M.G</creator><creator>BenMohamed, Lbachir</creator><creator>Huang, Xuefei</creator><general>American Chemical Society</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20151016</creationdate><title>Significant Impact of Immunogen Design on the Diversity of Antibodies Generated by Carbohydrate-Based Anticancer Vaccine</title><author>Yin, Zhaojun ; Chowdhury, Sudipa ; McKay, Craig ; Baniel, Claire ; Wright, W. Shea ; Bentley, Philip ; Kaczanowska, Katarzyna ; Gildersleeve, Jeffrey C ; Finn, M.G ; BenMohamed, Lbachir ; Huang, Xuefei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a441t-95f4924b338b25745e8b1eebbda71f6c4454543d70f0ca5641cbb5bf9a3c2d773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antibodies - blood</topic><topic>Antibodies - classification</topic><topic>Antigens, Tumor-Associated, Carbohydrate - immunology</topic><topic>Cancer Vaccines - chemistry</topic><topic>Cancer Vaccines - immunology</topic><topic>Disease Models, Animal</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Immunotherapy</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yin, Zhaojun</creatorcontrib><creatorcontrib>Chowdhury, Sudipa</creatorcontrib><creatorcontrib>McKay, Craig</creatorcontrib><creatorcontrib>Baniel, Claire</creatorcontrib><creatorcontrib>Wright, W. Shea</creatorcontrib><creatorcontrib>Bentley, Philip</creatorcontrib><creatorcontrib>Kaczanowska, Katarzyna</creatorcontrib><creatorcontrib>Gildersleeve, Jeffrey C</creatorcontrib><creatorcontrib>Finn, M.G</creatorcontrib><creatorcontrib>BenMohamed, Lbachir</creatorcontrib><creatorcontrib>Huang, Xuefei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>ACS chemical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yin, Zhaojun</au><au>Chowdhury, Sudipa</au><au>McKay, Craig</au><au>Baniel, Claire</au><au>Wright, W. Shea</au><au>Bentley, Philip</au><au>Kaczanowska, Katarzyna</au><au>Gildersleeve, Jeffrey C</au><au>Finn, M.G</au><au>BenMohamed, Lbachir</au><au>Huang, Xuefei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Significant Impact of Immunogen Design on the Diversity of Antibodies Generated by Carbohydrate-Based Anticancer Vaccine</atitle><jtitle>ACS chemical biology</jtitle><addtitle>ACS Chem. Biol</addtitle><date>2015-10-16</date><risdate>2015</risdate><volume>10</volume><issue>10</issue><spage>2364</spage><epage>2372</epage><pages>2364-2372</pages><issn>1554-8929</issn><eissn>1554-8937</eissn><abstract>Development of an effective vaccine targeting tumor associated carbohydrate antigens (TACAs) is an appealing approach toward tumor immunotherapy. While much emphasis has been typically placed on generating high antibody titers against the immunizing antigen, the impact of immunogen design on the diversity of TACA-specific antibodies elicited has been overlooked. Herein, we report that the immunogen structure can significantly impact the breadth and the magnitude of humoral responses. Vaccine constructs that induced diverse TACA-binding antibodies provided much stronger recognition of a variety of Tn positive tumor cells. Optimization of the breadth of the antibody response led to a vaccine construct that demonstrated long lasting efficacy in a mouse tumor model. After challenged with the highly aggressive TA3Ha cells, mice immunized with the new construct exhibited a statistically significant improvement in survival relative to controls (0% vs 50% survival; p &lt; 0.0001). Furthermore, the surviving mice developed long-term immunity against TA3Ha. Thus, both the magnitude and the breadth of antibody reactivity should be considered when designing TACA-based antitumor vaccines.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>26262839</pmid><doi>10.1021/acschembio.5b00406</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1554-8929
ispartof ACS chemical biology, 2015-10, Vol.10 (10), p.2364-2372
issn 1554-8929
1554-8937
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4725323
source American Chemical Society; MEDLINE
subjects Animals
Antibodies - blood
Antibodies - classification
Antigens, Tumor-Associated, Carbohydrate - immunology
Cancer Vaccines - chemistry
Cancer Vaccines - immunology
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Immunotherapy
Mice
Mice, Inbred C57BL
title Significant Impact of Immunogen Design on the Diversity of Antibodies Generated by Carbohydrate-Based Anticancer Vaccine
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T11%3A51%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Significant%20Impact%20of%20Immunogen%20Design%20on%20the%20Diversity%20of%20Antibodies%20Generated%20by%20Carbohydrate-Based%20Anticancer%20Vaccine&rft.jtitle=ACS%20chemical%20biology&rft.au=Yin,%20Zhaojun&rft.date=2015-10-16&rft.volume=10&rft.issue=10&rft.spage=2364&rft.epage=2372&rft.pages=2364-2372&rft.issn=1554-8929&rft.eissn=1554-8937&rft_id=info:doi/10.1021/acschembio.5b00406&rft_dat=%3Cproquest_pubme%3E1722928428%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1722928428&rft_id=info:pmid/26262839&rfr_iscdi=true