A liposome-based cancer vaccine for a rapid and high-titre anti-ErbB-2 antibody response
Vaccines are arguably the most important medical technology developed to date. However, effective treatment of diseases such as breast cancer have so far evaded standard vaccination strategies. One popular target for cancer treatment is the cell surface membrane protein, ErbB-2, also known as Her-2...
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Veröffentlicht in: | European journal of pharmaceutical sciences 2020-09, Vol.152, p.105456-105456, Article 105456 |
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creator | Wallis, Jamie Katti, Prateek Martin, Alexander M. Hills, Tom Seymour, Leonard W. Shenton, Daniel P. Carlisle, Robert C. |
description | Vaccines are arguably the most important medical technology developed to date. However, effective treatment of diseases such as breast cancer have so far evaded standard vaccination strategies. One popular target for cancer treatment is the cell surface membrane protein, ErbB-2, also known as Her-2 or neu. It is localised to the cell surface and has raised expression in 15–30% of all breast cancers, as well as in ovarian, colon and lung cancer. Here, a liposomal system comprised of spatially separated ErbB-2 peptide, to activate B cells, and ovalbumin peptide OVA323−339, to provide non-cognate T cell support, was used to generate antibodies against the epitope of the ErbB-2 protein targeted by Pertuzumab, a monoclonal antibody licensed for the treatment of ErbB-2 expressing cancers. After just 7 days a raised (7.3-fold, p |
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[Display omitted]</description><identifier>ISSN: 0928-0987</identifier><identifier>EISSN: 1879-0720</identifier><identifier>DOI: 10.1016/j.ejps.2020.105456</identifier><identifier>PMID: 32653563</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Antibodies, Monoclonal ; Antibody Formation ; Cancer ; Cancer Vaccines ; Cell Line, Tumor ; ErbB2 ; Her2 ; Liposome ; Liposomes ; Mice ; Neoplasms - drug therapy ; Receptor, ErbB-2 ; Vaccination ; Vaccine</subject><ispartof>European journal of pharmaceutical sciences, 2020-09, Vol.152, p.105456-105456, Article 105456</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-d30e8c90ecc54494f57dea42b7c31845fdb3f4c7a6f74896a4364ff6aa266ae03</citedby><cites>FETCH-LOGICAL-c400t-d30e8c90ecc54494f57dea42b7c31845fdb3f4c7a6f74896a4364ff6aa266ae03</cites><orcidid>0000-0003-0322-5822 ; 0000-0003-4508-4802</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0928098720302451$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32653563$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wallis, Jamie</creatorcontrib><creatorcontrib>Katti, Prateek</creatorcontrib><creatorcontrib>Martin, Alexander M.</creatorcontrib><creatorcontrib>Hills, Tom</creatorcontrib><creatorcontrib>Seymour, Leonard W.</creatorcontrib><creatorcontrib>Shenton, Daniel P.</creatorcontrib><creatorcontrib>Carlisle, Robert C.</creatorcontrib><title>A liposome-based cancer vaccine for a rapid and high-titre anti-ErbB-2 antibody response</title><title>European journal of pharmaceutical sciences</title><addtitle>Eur J Pharm Sci</addtitle><description>Vaccines are arguably the most important medical technology developed to date. However, effective treatment of diseases such as breast cancer have so far evaded standard vaccination strategies. One popular target for cancer treatment is the cell surface membrane protein, ErbB-2, also known as Her-2 or neu. It is localised to the cell surface and has raised expression in 15–30% of all breast cancers, as well as in ovarian, colon and lung cancer. Here, a liposomal system comprised of spatially separated ErbB-2 peptide, to activate B cells, and ovalbumin peptide OVA323−339, to provide non-cognate T cell support, was used to generate antibodies against the epitope of the ErbB-2 protein targeted by Pertuzumab, a monoclonal antibody licensed for the treatment of ErbB-2 expressing cancers. After just 7 days a raised (7.3-fold, p<0.01), isotype-switched, humoral immune response specific for the ErbB-2 peptide was achieved in mice with pre-existing immunity to OVA which were exposed to liposomes with external ErbB-2 and internal OVA323−339. The absence of pre-existing OVA immunity in the mice or OVA323−339 peptide in the liposomes removed the effect. The effect of this anti-ErbB-2 antibody response was characterised against an ErbB-2 overexpressing tumour cell line both in vitro and in vivo. Notably, antibody responses were demonstrated to induce cell death in vitro, resulting in 96% reduction in viable cells. This study, therefore, demonstrates the feasibility of this approach to generate a rapid, high-titre, isotype-switched, antibody response that specifically targets ErbB-2 overexpression on tumour cells and is capable of inducing cell death in vitro in the absence of complement or immune cells.
[Display omitted]</description><subject>Animals</subject><subject>Antibodies, Monoclonal</subject><subject>Antibody Formation</subject><subject>Cancer</subject><subject>Cancer Vaccines</subject><subject>Cell Line, Tumor</subject><subject>ErbB2</subject><subject>Her2</subject><subject>Liposome</subject><subject>Liposomes</subject><subject>Mice</subject><subject>Neoplasms - drug therapy</subject><subject>Receptor, ErbB-2</subject><subject>Vaccination</subject><subject>Vaccine</subject><issn>0928-0987</issn><issn>1879-0720</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LJDEQhsPiss6O_gEPkqOXjNX56m7woqKrMOBlF_YW0klFM8x02qRH8N_b46hHT_XBUy_UQ8hJBYsKKn2-WuBqKAsOfLdQUukfZFY1dcug5nBAZtDyhkHb1IfkdykrANBNDb_IoeBaCaXFjPy_pOs4pJI2yDpb0FNne4eZvljnYo80pEwtzXaIntre06f4-MTGOGacxjGym9xdMf7ed8m_0oxlSH3BI_Iz2HXB4486J_9ub_5e37Hlw5_768slcxJgZF4ANq4FdE5J2cqgao9W8q52omqkCr4TQbra6lDLptVWCi1D0NZyrS2CmJOzfe6Q0_MWy2g2sThcr22PaVsMl1yoSreqnVC-R11OpWQMZshxY_OrqcDsjJqV2Rk1O6Nmb3Q6Ov3I33Yb9F8nnwon4GIP4PTlS8Rsios4OfQxoxuNT_G7_DdK1Ia3</recordid><startdate>20200901</startdate><enddate>20200901</enddate><creator>Wallis, Jamie</creator><creator>Katti, Prateek</creator><creator>Martin, Alexander M.</creator><creator>Hills, Tom</creator><creator>Seymour, Leonard W.</creator><creator>Shenton, Daniel P.</creator><creator>Carlisle, Robert C.</creator><general>Elsevier 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>7X8</scope><orcidid>https://orcid.org/0000-0003-0322-5822</orcidid><orcidid>https://orcid.org/0000-0003-4508-4802</orcidid></search><sort><creationdate>20200901</creationdate><title>A liposome-based cancer vaccine for a rapid and high-titre anti-ErbB-2 antibody response</title><author>Wallis, Jamie ; Katti, Prateek ; Martin, Alexander M. ; Hills, Tom ; Seymour, Leonard W. ; Shenton, Daniel P. ; Carlisle, Robert C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-d30e8c90ecc54494f57dea42b7c31845fdb3f4c7a6f74896a4364ff6aa266ae03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal</topic><topic>Antibody Formation</topic><topic>Cancer</topic><topic>Cancer Vaccines</topic><topic>Cell Line, Tumor</topic><topic>ErbB2</topic><topic>Her2</topic><topic>Liposome</topic><topic>Liposomes</topic><topic>Mice</topic><topic>Neoplasms - drug therapy</topic><topic>Receptor, ErbB-2</topic><topic>Vaccination</topic><topic>Vaccine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wallis, Jamie</creatorcontrib><creatorcontrib>Katti, Prateek</creatorcontrib><creatorcontrib>Martin, Alexander M.</creatorcontrib><creatorcontrib>Hills, Tom</creatorcontrib><creatorcontrib>Seymour, Leonard W.</creatorcontrib><creatorcontrib>Shenton, Daniel P.</creatorcontrib><creatorcontrib>Carlisle, Robert C.</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><jtitle>European journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wallis, Jamie</au><au>Katti, Prateek</au><au>Martin, Alexander M.</au><au>Hills, Tom</au><au>Seymour, Leonard W.</au><au>Shenton, Daniel P.</au><au>Carlisle, Robert C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A liposome-based cancer vaccine for a rapid and high-titre anti-ErbB-2 antibody response</atitle><jtitle>European journal of pharmaceutical sciences</jtitle><addtitle>Eur J Pharm Sci</addtitle><date>2020-09-01</date><risdate>2020</risdate><volume>152</volume><spage>105456</spage><epage>105456</epage><pages>105456-105456</pages><artnum>105456</artnum><issn>0928-0987</issn><eissn>1879-0720</eissn><abstract>Vaccines are arguably the most important medical technology developed to date. However, effective treatment of diseases such as breast cancer have so far evaded standard vaccination strategies. One popular target for cancer treatment is the cell surface membrane protein, ErbB-2, also known as Her-2 or neu. It is localised to the cell surface and has raised expression in 15–30% of all breast cancers, as well as in ovarian, colon and lung cancer. Here, a liposomal system comprised of spatially separated ErbB-2 peptide, to activate B cells, and ovalbumin peptide OVA323−339, to provide non-cognate T cell support, was used to generate antibodies against the epitope of the ErbB-2 protein targeted by Pertuzumab, a monoclonal antibody licensed for the treatment of ErbB-2 expressing cancers. After just 7 days a raised (7.3-fold, p<0.01), isotype-switched, humoral immune response specific for the ErbB-2 peptide was achieved in mice with pre-existing immunity to OVA which were exposed to liposomes with external ErbB-2 and internal OVA323−339. The absence of pre-existing OVA immunity in the mice or OVA323−339 peptide in the liposomes removed the effect. The effect of this anti-ErbB-2 antibody response was characterised against an ErbB-2 overexpressing tumour cell line both in vitro and in vivo. Notably, antibody responses were demonstrated to induce cell death in vitro, resulting in 96% reduction in viable cells. This study, therefore, demonstrates the feasibility of this approach to generate a rapid, high-titre, isotype-switched, antibody response that specifically targets ErbB-2 overexpression on tumour cells and is capable of inducing cell death in vitro in the absence of complement or immune cells.
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subjects | Animals Antibodies, Monoclonal Antibody Formation Cancer Cancer Vaccines Cell Line, Tumor ErbB2 Her2 Liposome Liposomes Mice Neoplasms - drug therapy Receptor, ErbB-2 Vaccination Vaccine |
title | A liposome-based cancer vaccine for a rapid and high-titre anti-ErbB-2 antibody response |
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