Preclinical Evaluation of virus-like particle Vaccine Against Carbonic Anhydrase IX Efficacy in a Mouse Breast Cancer Model System
Carbonic anhydrase IX (CAIX) is a cancer-associated membrane protein frequently overexpressed in hypoxic solid tumours leading to enhanced tumour cell survival and invasion, and it has been proposed to be an attractive tumour-specific molecule for antibody-mediated targeting. This study aimed to gen...
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Veröffentlicht in: | Molecular biotechnology 2024-05, Vol.66 (5), p.1206-1219 |
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creator | Kalniņa, Zane Liekniņa, Ilva Skeltona, Vendija Akopjana, Ināra Kazāks, Andris Tārs, Kaspars |
description | Carbonic anhydrase IX (CAIX) is a cancer-associated membrane protein frequently overexpressed in hypoxic solid tumours leading to enhanced tumour cell survival and invasion, and it has been proposed to be an attractive tumour-specific molecule for antibody-mediated targeting. This study aimed to generate a virus-like particle (VLP)-based CAIX vaccine candidate and evaluate its efficacy in a mouse model of breast cancer. The prototype murine vaccine was developed based on the ssRNA bacteriophage Qbeta VLPs with chemically coupled murine CAIX protein catalytic domains on their surfaces. The vaccine was shown to efficiently break the natural B cell tolerance against autologous murine CAIX and to induce high-titre Th1-oriented IgG responses in the BALB/c mice
.
This vaccine was tested in a therapeutic setting by using a triple-negative breast cancer mouse model system comprising 4T1, 4T1-
Car9
KI
and 4T1-
Car9
KO
cells, the latter representing positive and negative controls for murine CAIX production, respectively. The humoural immune responses induced in tumour-bearing animals were predominantly of Th1-type and higher anti-mCAIXc titres correlated with slower growth and lung metastasis development of 4T1 tumours constitutively expressing mCAIX in vivo in the syngeneic host. |
doi_str_mv | 10.1007/s12033-023-01021-5 |
format | Article |
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.
This vaccine was tested in a therapeutic setting by using a triple-negative breast cancer mouse model system comprising 4T1, 4T1-
Car9
KI
and 4T1-
Car9
KO
cells, the latter representing positive and negative controls for murine CAIX production, respectively. The humoural immune responses induced in tumour-bearing animals were predominantly of Th1-type and higher anti-mCAIXc titres correlated with slower growth and lung metastasis development of 4T1 tumours constitutively expressing mCAIX in vivo in the syngeneic host.</description><identifier>ISSN: 1073-6085</identifier><identifier>EISSN: 1559-0305</identifier><identifier>DOI: 10.1007/s12033-023-01021-5</identifier><identifier>PMID: 38217826</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Antigens, Neoplasm - genetics ; Antigens, Neoplasm - immunology ; Biochemistry ; Biological Techniques ; Biotechnology ; Breast cancer ; Breast Neoplasms - immunology ; Breast Neoplasms - therapy ; Cancer vaccines ; Cancer Vaccines - immunology ; Carbonic anhydrase ; Carbonic Anhydrase IX - genetics ; Carbonic Anhydrase IX - immunology ; Carbonic Anhydrase IX - metabolism ; Carbonic anhydrases ; Cell Biology ; Cell Line, Tumor ; Cell survival ; Chemistry ; Chemistry and Materials Science ; Disease Models, Animal ; Effectiveness ; Female ; Human Genetics ; Humans ; Hypoxia ; Immunoglobulin G ; Immunological tolerance ; Lymphocytes T ; Membrane proteins ; Metastases ; Mice ; Mice, Inbred BALB C ; Original Paper ; Phages ; Protein Science ; Proteins ; Solid tumors ; Tumors ; Vaccines ; Vaccines, Virus-Like Particle - immunology ; Virus-like particles</subject><ispartof>Molecular biotechnology, 2024-05, Vol.66 (5), p.1206-1219</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-32f2b31ed303f15030ca53e6520c7b9b1572e3acc738c3b4178b152bcb5cee593</cites><orcidid>0000-0001-9002-3131</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/s12033-023-01021-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12033-023-01021-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38217826$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kalniņa, Zane</creatorcontrib><creatorcontrib>Liekniņa, Ilva</creatorcontrib><creatorcontrib>Skeltona, Vendija</creatorcontrib><creatorcontrib>Akopjana, Ināra</creatorcontrib><creatorcontrib>Kazāks, Andris</creatorcontrib><creatorcontrib>Tārs, Kaspars</creatorcontrib><title>Preclinical Evaluation of virus-like particle Vaccine Against Carbonic Anhydrase IX Efficacy in a Mouse Breast Cancer Model System</title><title>Molecular biotechnology</title><addtitle>Mol Biotechnol</addtitle><addtitle>Mol Biotechnol</addtitle><description>Carbonic anhydrase IX (CAIX) is a cancer-associated membrane protein frequently overexpressed in hypoxic solid tumours leading to enhanced tumour cell survival and invasion, and it has been proposed to be an attractive tumour-specific molecule for antibody-mediated targeting. This study aimed to generate a virus-like particle (VLP)-based CAIX vaccine candidate and evaluate its efficacy in a mouse model of breast cancer. The prototype murine vaccine was developed based on the ssRNA bacteriophage Qbeta VLPs with chemically coupled murine CAIX protein catalytic domains on their surfaces. The vaccine was shown to efficiently break the natural B cell tolerance against autologous murine CAIX and to induce high-titre Th1-oriented IgG responses in the BALB/c mice
.
This vaccine was tested in a therapeutic setting by using a triple-negative breast cancer mouse model system comprising 4T1, 4T1-
Car9
KI
and 4T1-
Car9
KO
cells, the latter representing positive and negative controls for murine CAIX production, respectively. The humoural immune responses induced in tumour-bearing animals were predominantly of Th1-type and higher anti-mCAIXc titres correlated with slower growth and lung metastasis development of 4T1 tumours constitutively expressing mCAIX in vivo in the syngeneic host.</description><subject>Animals</subject><subject>Antigens, Neoplasm - genetics</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Biochemistry</subject><subject>Biological Techniques</subject><subject>Biotechnology</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - immunology</subject><subject>Breast Neoplasms - therapy</subject><subject>Cancer vaccines</subject><subject>Cancer Vaccines - immunology</subject><subject>Carbonic anhydrase</subject><subject>Carbonic Anhydrase IX - genetics</subject><subject>Carbonic Anhydrase IX - immunology</subject><subject>Carbonic Anhydrase IX - metabolism</subject><subject>Carbonic anhydrases</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Cell survival</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Disease Models, Animal</subject><subject>Effectiveness</subject><subject>Female</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Immunoglobulin G</subject><subject>Immunological tolerance</subject><subject>Lymphocytes T</subject><subject>Membrane proteins</subject><subject>Metastases</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Original Paper</subject><subject>Phages</subject><subject>Protein Science</subject><subject>Proteins</subject><subject>Solid tumors</subject><subject>Tumors</subject><subject>Vaccines</subject><subject>Vaccines, Virus-Like Particle - immunology</subject><subject>Virus-like particles</subject><issn>1073-6085</issn><issn>1559-0305</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1PGzEUtFARUMof4IAs9cJli-2Hd7PHEAWKBKJSP8TN8jpvwdTxBnsXKVd-OS8JtBIHDpat8cx4noexQym-SSGqkyyVACiEoiWFkoXeYntS67oQIPQnOosKilKM9C77nPODII4-hR22CyMlq5Eq99jzj4Qu-OidDXz6ZMNge99F3rX8yachF8H_Rb6wqfcuIP9jnfMR-fjO-ph7PrGp6UjMx_F-OUs2I7-85dO2JT-35D5yy6-7geCzhHYtiA4TYTMM_Ocy9zj_wrZbGzIevO777Pf59Nfke3F1c3E5GV8VDlTZF6Ba1YDEGQhopaYRndWApVbCVU3dSF0pBMpXwchBc0oDEqYa12iHqGvYZ8cb30XqHgfMvZn77DAEG5EiGlWrWoCqdUnUr--oD92QIqUz9LMAWmm5MlQblktdzglbs0h-btPSSGFWDZlNQ4YaMuuGjCbR0av10Mxx9k_yVgkRYEPIdBXvMP1_-wPbF_2rmyk</recordid><startdate>20240501</startdate><enddate>20240501</enddate><creator>Kalniņa, Zane</creator><creator>Liekniņa, Ilva</creator><creator>Skeltona, Vendija</creator><creator>Akopjana, Ināra</creator><creator>Kazāks, Andris</creator><creator>Tārs, Kaspars</creator><general>Springer US</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>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9002-3131</orcidid></search><sort><creationdate>20240501</creationdate><title>Preclinical Evaluation of virus-like particle Vaccine Against Carbonic Anhydrase IX Efficacy in a Mouse Breast Cancer Model System</title><author>Kalniņa, Zane ; Liekniņa, Ilva ; Skeltona, Vendija ; Akopjana, Ināra ; Kazāks, Andris ; Tārs, Kaspars</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c326t-32f2b31ed303f15030ca53e6520c7b9b1572e3acc738c3b4178b152bcb5cee593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Antigens, Neoplasm - genetics</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Biochemistry</topic><topic>Biological Techniques</topic><topic>Biotechnology</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - immunology</topic><topic>Breast Neoplasms - therapy</topic><topic>Cancer vaccines</topic><topic>Cancer Vaccines - immunology</topic><topic>Carbonic anhydrase</topic><topic>Carbonic Anhydrase IX - genetics</topic><topic>Carbonic Anhydrase IX - immunology</topic><topic>Carbonic Anhydrase IX - metabolism</topic><topic>Carbonic anhydrases</topic><topic>Cell Biology</topic><topic>Cell Line, Tumor</topic><topic>Cell survival</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Disease Models, Animal</topic><topic>Effectiveness</topic><topic>Female</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Immunoglobulin G</topic><topic>Immunological tolerance</topic><topic>Lymphocytes T</topic><topic>Membrane proteins</topic><topic>Metastases</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Original Paper</topic><topic>Phages</topic><topic>Protein Science</topic><topic>Proteins</topic><topic>Solid tumors</topic><topic>Tumors</topic><topic>Vaccines</topic><topic>Vaccines, Virus-Like Particle - immunology</topic><topic>Virus-like particles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kalniņa, Zane</creatorcontrib><creatorcontrib>Liekniņa, Ilva</creatorcontrib><creatorcontrib>Skeltona, Vendija</creatorcontrib><creatorcontrib>Akopjana, Ināra</creatorcontrib><creatorcontrib>Kazāks, Andris</creatorcontrib><creatorcontrib>Tārs, Kaspars</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kalniņa, Zane</au><au>Liekniņa, Ilva</au><au>Skeltona, Vendija</au><au>Akopjana, Ināra</au><au>Kazāks, Andris</au><au>Tārs, Kaspars</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preclinical Evaluation of virus-like particle Vaccine Against Carbonic Anhydrase IX Efficacy in a Mouse Breast Cancer Model System</atitle><jtitle>Molecular biotechnology</jtitle><stitle>Mol Biotechnol</stitle><addtitle>Mol Biotechnol</addtitle><date>2024-05-01</date><risdate>2024</risdate><volume>66</volume><issue>5</issue><spage>1206</spage><epage>1219</epage><pages>1206-1219</pages><issn>1073-6085</issn><eissn>1559-0305</eissn><abstract>Carbonic anhydrase IX (CAIX) is a cancer-associated membrane protein frequently overexpressed in hypoxic solid tumours leading to enhanced tumour cell survival and invasion, and it has been proposed to be an attractive tumour-specific molecule for antibody-mediated targeting. This study aimed to generate a virus-like particle (VLP)-based CAIX vaccine candidate and evaluate its efficacy in a mouse model of breast cancer. The prototype murine vaccine was developed based on the ssRNA bacteriophage Qbeta VLPs with chemically coupled murine CAIX protein catalytic domains on their surfaces. The vaccine was shown to efficiently break the natural B cell tolerance against autologous murine CAIX and to induce high-titre Th1-oriented IgG responses in the BALB/c mice
.
This vaccine was tested in a therapeutic setting by using a triple-negative breast cancer mouse model system comprising 4T1, 4T1-
Car9
KI
and 4T1-
Car9
KO
cells, the latter representing positive and negative controls for murine CAIX production, respectively. The humoural immune responses induced in tumour-bearing animals were predominantly of Th1-type and higher anti-mCAIXc titres correlated with slower growth and lung metastasis development of 4T1 tumours constitutively expressing mCAIX in vivo in the syngeneic host.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>38217826</pmid><doi>10.1007/s12033-023-01021-5</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-9002-3131</orcidid></addata></record> |
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subjects | Animals Antigens, Neoplasm - genetics Antigens, Neoplasm - immunology Biochemistry Biological Techniques Biotechnology Breast cancer Breast Neoplasms - immunology Breast Neoplasms - therapy Cancer vaccines Cancer Vaccines - immunology Carbonic anhydrase Carbonic Anhydrase IX - genetics Carbonic Anhydrase IX - immunology Carbonic Anhydrase IX - metabolism Carbonic anhydrases Cell Biology Cell Line, Tumor Cell survival Chemistry Chemistry and Materials Science Disease Models, Animal Effectiveness Female Human Genetics Humans Hypoxia Immunoglobulin G Immunological tolerance Lymphocytes T Membrane proteins Metastases Mice Mice, Inbred BALB C Original Paper Phages Protein Science Proteins Solid tumors Tumors Vaccines Vaccines, Virus-Like Particle - immunology Virus-like particles |
title | Preclinical Evaluation of virus-like particle Vaccine Against Carbonic Anhydrase IX Efficacy in a Mouse Breast Cancer Model System |
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