Vaccination with liposome-coupled glypican-3-derived epitope peptide stimulates cytotoxic T lymphocytes and inhibits GPC3-expressing tumor growth in mice
Because therapeutic manipulation of immunity can induce tumor regression, anti-cancer immunotherapy is considered a promising treatment modality. We previously reported that glypican-3 (GPC3), an oncofetal antigen overexpressed in hepatocellular carcinoma (HCC), is a useful target for cytotoxic T ly...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2016-01, Vol.469 (1), p.138-143 |
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| creator | Iwama, Tatsuaki Uchida, Tetsuya Sawada, Yu Tsuchiya, Nobuhiro Sugai, Shiori Fujinami, Norihiro Shimomura, Manami Yoshikawa, Toshiaki Zhang, Rong Uemura, Yasushi Nakatsura, Tetsuya |
| description | Because therapeutic manipulation of immunity can induce tumor regression, anti-cancer immunotherapy is considered a promising treatment modality. We previously reported that glypican-3 (GPC3), an oncofetal antigen overexpressed in hepatocellular carcinoma (HCC), is a useful target for cytotoxic T lymphocyte (CTL)-mediated cancer immunotherapy, and we have performed clinical trials using the GPC3-derived peptide vaccine. Although vaccine-induced GPC3-peptide-specific CTLs were often tumor reactive in vitro and were correlated with overall survival, no complete response was observed. In the current study, we synthesized liposome-coupled GPC3-derived CTL epitope peptide (pGPC3-lipsome) and investigated its antitumor potential. Vaccination with pGPC3-liposome induced peptide-specific CTLs at a lower dose than conventional vaccine emulsified in incomplete Freund's adjuvant. Coupling of pGPC3 to liposomes was essential for effective priming of GPC3-specific CTLs. In addition, immunization with pGPC3-liposome inhibited GPC3-expressing tumor growth. Thus, vaccination with tumor-associated antigen-derived epitope peptides coupled to the surfaces of liposomes may be a novel therapeutic strategy for cancer. |
| doi_str_mv | 10.1016/j.bbrc.2015.11.084 |
| format | Article |
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We previously reported that glypican-3 (GPC3), an oncofetal antigen overexpressed in hepatocellular carcinoma (HCC), is a useful target for cytotoxic T lymphocyte (CTL)-mediated cancer immunotherapy, and we have performed clinical trials using the GPC3-derived peptide vaccine. Although vaccine-induced GPC3-peptide-specific CTLs were often tumor reactive in vitro and were correlated with overall survival, no complete response was observed. In the current study, we synthesized liposome-coupled GPC3-derived CTL epitope peptide (pGPC3-lipsome) and investigated its antitumor potential. Vaccination with pGPC3-liposome induced peptide-specific CTLs at a lower dose than conventional vaccine emulsified in incomplete Freund's adjuvant. Coupling of pGPC3 to liposomes was essential for effective priming of GPC3-specific CTLs. In addition, immunization with pGPC3-liposome inhibited GPC3-expressing tumor growth. Thus, vaccination with tumor-associated antigen-derived epitope peptides coupled to the surfaces of liposomes may be a novel therapeutic strategy for cancer.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2015.11.084</identifier><identifier>PMID: 26616051</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>A2-Tg mouse ; adjuvants ; Animals ; antineoplastic activity ; APC ; BM-DC ; Cancer ; Cancer Vaccines - administration & dosage ; Cancer Vaccines - immunology ; Cell Line, Tumor ; Cell Proliferation - drug effects ; clinical trials ; CpG ODN ; CTL ; cytotoxic T-lymphocytes ; cytotoxicity ; DMSO ; ELISpot assay ; epitopes ; Epitopes, T-Lymphocyte - immunology ; FBS ; Glypican-3 ; Glypicans - immunology ; GPC3 ; HCC ; Hepatocellular carcinoma ; hepatoma ; IFA ; immunity ; Immunotherapy ; Liposome ; Liposomes ; Lymphocyte Activation - drug effects ; Lymphocyte Activation - immunology ; mGM-CSF ; MHC ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasms, Experimental - immunology ; Neoplasms, Experimental - pathology ; Neoplasms, Experimental - therapy ; OVA ; Peptide vaccine ; peptides ; Peptides - administration & dosage ; Peptides - immunology ; pGPC3 ; pGPC3(A2) ; pGPC3(A2)-liposome/CpG ; pGPC3(B6) ; pGPC3(B6)-liposome/CpG ; pGPC3-liposome ; remission ; SPF ; T-Lymphocytes, Cytotoxic - drug effects ; T-Lymphocytes, Cytotoxic - immunology ; TAA ; TAP ; TLR9 ; Treatment Outcome ; vaccination ; Vaccination - methods ; vaccines</subject><ispartof>Biochemical and biophysical research communications, 2016-01, Vol.469 (1), p.138-143</ispartof><rights>2015 The Authors</rights><rights>Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c457t-62efd6ed6e00c8d27229ba2c8b418484ec9c867243d472b4d34fbc0049d49e4f3</citedby><cites>FETCH-LOGICAL-c457t-62efd6ed6e00c8d27229ba2c8b418484ec9c867243d472b4d34fbc0049d49e4f3</cites><orcidid>0000-0003-4437-316X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2015.11.084$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,4024,27923,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26616051$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iwama, Tatsuaki</creatorcontrib><creatorcontrib>Uchida, Tetsuya</creatorcontrib><creatorcontrib>Sawada, Yu</creatorcontrib><creatorcontrib>Tsuchiya, Nobuhiro</creatorcontrib><creatorcontrib>Sugai, Shiori</creatorcontrib><creatorcontrib>Fujinami, Norihiro</creatorcontrib><creatorcontrib>Shimomura, Manami</creatorcontrib><creatorcontrib>Yoshikawa, Toshiaki</creatorcontrib><creatorcontrib>Zhang, Rong</creatorcontrib><creatorcontrib>Uemura, Yasushi</creatorcontrib><creatorcontrib>Nakatsura, Tetsuya</creatorcontrib><title>Vaccination with liposome-coupled glypican-3-derived epitope peptide stimulates cytotoxic T lymphocytes and inhibits GPC3-expressing tumor growth in mice</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Because therapeutic manipulation of immunity can induce tumor regression, anti-cancer immunotherapy is considered a promising treatment modality. We previously reported that glypican-3 (GPC3), an oncofetal antigen overexpressed in hepatocellular carcinoma (HCC), is a useful target for cytotoxic T lymphocyte (CTL)-mediated cancer immunotherapy, and we have performed clinical trials using the GPC3-derived peptide vaccine. Although vaccine-induced GPC3-peptide-specific CTLs were often tumor reactive in vitro and were correlated with overall survival, no complete response was observed. In the current study, we synthesized liposome-coupled GPC3-derived CTL epitope peptide (pGPC3-lipsome) and investigated its antitumor potential. Vaccination with pGPC3-liposome induced peptide-specific CTLs at a lower dose than conventional vaccine emulsified in incomplete Freund's adjuvant. Coupling of pGPC3 to liposomes was essential for effective priming of GPC3-specific CTLs. In addition, immunization with pGPC3-liposome inhibited GPC3-expressing tumor growth. Thus, vaccination with tumor-associated antigen-derived epitope peptides coupled to the surfaces of liposomes may be a novel therapeutic strategy for cancer.</description><subject>A2-Tg mouse</subject><subject>adjuvants</subject><subject>Animals</subject><subject>antineoplastic activity</subject><subject>APC</subject><subject>BM-DC</subject><subject>Cancer</subject><subject>Cancer Vaccines - administration & dosage</subject><subject>Cancer Vaccines - immunology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>clinical trials</subject><subject>CpG ODN</subject><subject>CTL</subject><subject>cytotoxic T-lymphocytes</subject><subject>cytotoxicity</subject><subject>DMSO</subject><subject>ELISpot assay</subject><subject>epitopes</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>FBS</subject><subject>Glypican-3</subject><subject>Glypicans - immunology</subject><subject>GPC3</subject><subject>HCC</subject><subject>Hepatocellular carcinoma</subject><subject>hepatoma</subject><subject>IFA</subject><subject>immunity</subject><subject>Immunotherapy</subject><subject>Liposome</subject><subject>Liposomes</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Lymphocyte Activation - immunology</subject><subject>mGM-CSF</subject><subject>MHC</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Neoplasms, Experimental - immunology</subject><subject>Neoplasms, Experimental - pathology</subject><subject>Neoplasms, Experimental - therapy</subject><subject>OVA</subject><subject>Peptide vaccine</subject><subject>peptides</subject><subject>Peptides - administration & dosage</subject><subject>Peptides - immunology</subject><subject>pGPC3</subject><subject>pGPC3(A2)</subject><subject>pGPC3(A2)-liposome/CpG</subject><subject>pGPC3(B6)</subject><subject>pGPC3(B6)-liposome/CpG</subject><subject>pGPC3-liposome</subject><subject>remission</subject><subject>SPF</subject><subject>T-Lymphocytes, Cytotoxic - drug effects</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>TAA</subject><subject>TAP</subject><subject>TLR9</subject><subject>Treatment Outcome</subject><subject>vaccination</subject><subject>Vaccination - methods</subject><subject>vaccines</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkdGK1DAUhoso7uzqC3ihufSmNUkzaQveyKC7woKCu-JdSJPTmTO0TUzS3Z1H8W3NMKuXIgQCP9_5OZyvKF4xWjHK5Lt91ffBVJyydcVYRVvxpFgx2tGSMyqeFitKqSx5x36cFecx7illTMjueXHGpWSSrtmq-PVdG4OzTuhmco9pR0b0LroJSuMWP4Il2_Hg0ei5rEsLAe9yBB6T80A8-IQWSEw4LaNOEIk5JJfcAxpyQ8bD5HcuJznXsyU477DHFMnl101dwoMPECPOW5KWyQWyDe4-L4AzmdDAi-LZoMcILx__i-L208ebzVV5_eXy8-bDdWnEukml5DBYCflRalrLG867XnPT9oK1ohVgOtPKhovaiob3wtZi6A2lorOiAzHUF8XbU68P7ucCMakJo4Fx1DO4JSrWSF6vu5bR_0DXGa1pe0T5CTXBxRhgUD7gpMNBMaqO9tReHe2poz3FmMr28tDrx_6ln8D-HfmjKwNvTsCgndLbgFHdfssNMqvtRNfUmXh_IiCf7A4hqGgQZgMWA5ikrMN_bfAbFUa3lQ</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Iwama, Tatsuaki</creator><creator>Uchida, Tetsuya</creator><creator>Sawada, Yu</creator><creator>Tsuchiya, Nobuhiro</creator><creator>Sugai, Shiori</creator><creator>Fujinami, Norihiro</creator><creator>Shimomura, Manami</creator><creator>Yoshikawa, Toshiaki</creator><creator>Zhang, Rong</creator><creator>Uemura, Yasushi</creator><creator>Nakatsura, Tetsuya</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><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>7T5</scope><scope>H94</scope><orcidid>https://orcid.org/0000-0003-4437-316X</orcidid></search><sort><creationdate>20160101</creationdate><title>Vaccination with liposome-coupled glypican-3-derived epitope peptide stimulates cytotoxic T lymphocytes and inhibits GPC3-expressing tumor growth in mice</title><author>Iwama, Tatsuaki ; Uchida, Tetsuya ; Sawada, Yu ; Tsuchiya, Nobuhiro ; Sugai, Shiori ; Fujinami, Norihiro ; Shimomura, Manami ; Yoshikawa, Toshiaki ; Zhang, Rong ; Uemura, Yasushi ; Nakatsura, Tetsuya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c457t-62efd6ed6e00c8d27229ba2c8b418484ec9c867243d472b4d34fbc0049d49e4f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>A2-Tg mouse</topic><topic>adjuvants</topic><topic>Animals</topic><topic>antineoplastic activity</topic><topic>APC</topic><topic>BM-DC</topic><topic>Cancer</topic><topic>Cancer Vaccines - administration & dosage</topic><topic>Cancer Vaccines - immunology</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>clinical trials</topic><topic>CpG ODN</topic><topic>CTL</topic><topic>cytotoxic T-lymphocytes</topic><topic>cytotoxicity</topic><topic>DMSO</topic><topic>ELISpot assay</topic><topic>epitopes</topic><topic>Epitopes, T-Lymphocyte - immunology</topic><topic>FBS</topic><topic>Glypican-3</topic><topic>Glypicans - immunology</topic><topic>GPC3</topic><topic>HCC</topic><topic>Hepatocellular carcinoma</topic><topic>hepatoma</topic><topic>IFA</topic><topic>immunity</topic><topic>Immunotherapy</topic><topic>Liposome</topic><topic>Liposomes</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Lymphocyte Activation - immunology</topic><topic>mGM-CSF</topic><topic>MHC</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Neoplasms, Experimental - immunology</topic><topic>Neoplasms, Experimental - pathology</topic><topic>Neoplasms, Experimental - therapy</topic><topic>OVA</topic><topic>Peptide vaccine</topic><topic>peptides</topic><topic>Peptides - administration & dosage</topic><topic>Peptides - immunology</topic><topic>pGPC3</topic><topic>pGPC3(A2)</topic><topic>pGPC3(A2)-liposome/CpG</topic><topic>pGPC3(B6)</topic><topic>pGPC3(B6)-liposome/CpG</topic><topic>pGPC3-liposome</topic><topic>remission</topic><topic>SPF</topic><topic>T-Lymphocytes, Cytotoxic - drug effects</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>TAA</topic><topic>TAP</topic><topic>TLR9</topic><topic>Treatment Outcome</topic><topic>vaccination</topic><topic>Vaccination - methods</topic><topic>vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iwama, Tatsuaki</creatorcontrib><creatorcontrib>Uchida, Tetsuya</creatorcontrib><creatorcontrib>Sawada, Yu</creatorcontrib><creatorcontrib>Tsuchiya, Nobuhiro</creatorcontrib><creatorcontrib>Sugai, Shiori</creatorcontrib><creatorcontrib>Fujinami, Norihiro</creatorcontrib><creatorcontrib>Shimomura, Manami</creatorcontrib><creatorcontrib>Yoshikawa, Toshiaki</creatorcontrib><creatorcontrib>Zhang, Rong</creatorcontrib><creatorcontrib>Uemura, Yasushi</creatorcontrib><creatorcontrib>Nakatsura, Tetsuya</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iwama, Tatsuaki</au><au>Uchida, Tetsuya</au><au>Sawada, Yu</au><au>Tsuchiya, Nobuhiro</au><au>Sugai, Shiori</au><au>Fujinami, Norihiro</au><au>Shimomura, Manami</au><au>Yoshikawa, Toshiaki</au><au>Zhang, Rong</au><au>Uemura, Yasushi</au><au>Nakatsura, Tetsuya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vaccination with liposome-coupled glypican-3-derived epitope peptide stimulates cytotoxic T lymphocytes and inhibits GPC3-expressing tumor growth in mice</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>469</volume><issue>1</issue><spage>138</spage><epage>143</epage><pages>138-143</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Because therapeutic manipulation of immunity can induce tumor regression, anti-cancer immunotherapy is considered a promising treatment modality. We previously reported that glypican-3 (GPC3), an oncofetal antigen overexpressed in hepatocellular carcinoma (HCC), is a useful target for cytotoxic T lymphocyte (CTL)-mediated cancer immunotherapy, and we have performed clinical trials using the GPC3-derived peptide vaccine. Although vaccine-induced GPC3-peptide-specific CTLs were often tumor reactive in vitro and were correlated with overall survival, no complete response was observed. In the current study, we synthesized liposome-coupled GPC3-derived CTL epitope peptide (pGPC3-lipsome) and investigated its antitumor potential. Vaccination with pGPC3-liposome induced peptide-specific CTLs at a lower dose than conventional vaccine emulsified in incomplete Freund's adjuvant. Coupling of pGPC3 to liposomes was essential for effective priming of GPC3-specific CTLs. In addition, immunization with pGPC3-liposome inhibited GPC3-expressing tumor growth. Thus, vaccination with tumor-associated antigen-derived epitope peptides coupled to the surfaces of liposomes may be a novel therapeutic strategy for cancer.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26616051</pmid><doi>10.1016/j.bbrc.2015.11.084</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0003-4437-316X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | A2-Tg mouse adjuvants Animals antineoplastic activity APC BM-DC Cancer Cancer Vaccines - administration & dosage Cancer Vaccines - immunology Cell Line, Tumor Cell Proliferation - drug effects clinical trials CpG ODN CTL cytotoxic T-lymphocytes cytotoxicity DMSO ELISpot assay epitopes Epitopes, T-Lymphocyte - immunology FBS Glypican-3 Glypicans - immunology GPC3 HCC Hepatocellular carcinoma hepatoma IFA immunity Immunotherapy Liposome Liposomes Lymphocyte Activation - drug effects Lymphocyte Activation - immunology mGM-CSF MHC Mice Mice, Inbred C57BL Mice, Knockout Neoplasms, Experimental - immunology Neoplasms, Experimental - pathology Neoplasms, Experimental - therapy OVA Peptide vaccine peptides Peptides - administration & dosage Peptides - immunology pGPC3 pGPC3(A2) pGPC3(A2)-liposome/CpG pGPC3(B6) pGPC3(B6)-liposome/CpG pGPC3-liposome remission SPF T-Lymphocytes, Cytotoxic - drug effects T-Lymphocytes, Cytotoxic - immunology TAA TAP TLR9 Treatment Outcome vaccination Vaccination - methods vaccines |
| title | Vaccination with liposome-coupled glypican-3-derived epitope peptide stimulates cytotoxic T lymphocytes and inhibits GPC3-expressing tumor growth in mice |
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