Phase I/II study of immunotherapy using tumor antigen-pulsed dendritic cells in patients with hepatocellular carcinoma
Dendritic cells (DCs) are increasingly used as adjuvants for vaccination strategies; however, there has been very little development in DC vaccines for patients with hepatocellular carcinoma (HCC). In this study, we assessed the safety, feasibility and efficacy of a multiple tumor-associated antigen...
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| Veröffentlicht in: | International journal of oncology 2012-11, Vol.41 (5), p.1601-1609 |
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| creator | TADA, FUJIMASA ABE, MASANORI HIROOKA, MASASHI IKEDA, YOSHIOU HIASA, YOICHI LEE, YOON JUNG, NAM-CHUL LEE, WOO-BOK LEE, HYUN-SOO BAE, YONG-SOO ONJI, MORIKAZU |
| description | Dendritic cells (DCs) are increasingly used as adjuvants for vaccination strategies; however, there has been very little development in DC vaccines for patients with hepatocellular carcinoma (HCC). In this study, we assessed the safety, feasibility and efficacy of a multiple tumor-associated antigen (TAA)-pulsed DC vaccine in 5 patients with advanced HCC. DCs were generated by culturing blood monocytes in the presence of granulocyte macrophage-colony stimulating factor and interleukin-4 for 5 days. The DC vaccine was prepared by pulsing DCs with cytoplasmic transduction peptide-attached α-fetoprotein, glypican-3 and MAGE-1 recombinant fusion proteins and cultivating them in the presence of maturation cocktail. DCs were injected subcutaneously near the inguinal lymph nodes, followed by topical application of toll-like receptor-7 agonist around the injection site. We showed that our DC vaccine was safe and well-tolerated over 6 vaccinations in 5 patients. All 5 patients showed T cell responses against TAAs. Clinical benefit was observed in one of the 5 patients. In conclusion, the feasibility, safety and immune activity of DCs pulsed with TAAs were confirmed in HCC patients. However, clinical response was detected only in one patient. Future trials may consider applying this therapy in a less advanced stage to obtain better clinical responses. |
| doi_str_mv | 10.3892/ijo.2012.1626 |
| format | Article |
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In this study, we assessed the safety, feasibility and efficacy of a multiple tumor-associated antigen (TAA)-pulsed DC vaccine in 5 patients with advanced HCC. DCs were generated by culturing blood monocytes in the presence of granulocyte macrophage-colony stimulating factor and interleukin-4 for 5 days. The DC vaccine was prepared by pulsing DCs with cytoplasmic transduction peptide-attached α-fetoprotein, glypican-3 and MAGE-1 recombinant fusion proteins and cultivating them in the presence of maturation cocktail. DCs were injected subcutaneously near the inguinal lymph nodes, followed by topical application of toll-like receptor-7 agonist around the injection site. We showed that our DC vaccine was safe and well-tolerated over 6 vaccinations in 5 patients. All 5 patients showed T cell responses against TAAs. Clinical benefit was observed in one of the 5 patients. In conclusion, the feasibility, safety and immune activity of DCs pulsed with TAAs were confirmed in HCC patients. However, clinical response was detected only in one patient. Future trials may consider applying this therapy in a less advanced stage to obtain better clinical responses.</description><identifier>ISSN: 1019-6439</identifier><identifier>EISSN: 1791-2423</identifier><identifier>DOI: 10.3892/ijo.2012.1626</identifier><identifier>PMID: 22971679</identifier><language>eng</language><publisher>Athens: D.A. Spandidos</publisher><subject>Aged ; Antigens, Neoplasm - immunology ; Biological and medical sciences ; Cancer Vaccines - adverse effects ; Cancer Vaccines - immunology ; Cancer Vaccines - therapeutic use ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - therapy ; clinical trial ; Cytokines - biosynthesis ; Cytokines - immunology ; dendritic cells ; Dendritic Cells - immunology ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Good Manufacturing Practice ; hepatocellular carcinoma ; Humans ; Immunotherapy ; Liver cancer ; Liver Neoplasms - pathology ; Liver Neoplasms - therapy ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Middle Aged ; Neoplasm Staging ; Rodents ; T cell receptors ; T-Lymphocytes - immunology ; Treatment Outcome ; Tumors ; Vaccines</subject><ispartof>International journal of oncology, 2012-11, Vol.41 (5), p.1601-1609</ispartof><rights>Copyright © 2012, Spandidos Publications</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Spandidos Publications UK Ltd. 2012</rights><rights>Copyright © 2012, Spandidos Publications 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-34e024003681db14c1eebc5ee17ce0f7e76778f61e1f0bbafac28de0642d43483</citedby><cites>FETCH-LOGICAL-c477t-34e024003681db14c1eebc5ee17ce0f7e76778f61e1f0bbafac28de0642d43483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,5571,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26430302$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22971679$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>TADA, FUJIMASA</creatorcontrib><creatorcontrib>ABE, MASANORI</creatorcontrib><creatorcontrib>HIROOKA, MASASHI</creatorcontrib><creatorcontrib>IKEDA, YOSHIOU</creatorcontrib><creatorcontrib>HIASA, YOICHI</creatorcontrib><creatorcontrib>LEE, YOON</creatorcontrib><creatorcontrib>JUNG, NAM-CHUL</creatorcontrib><creatorcontrib>LEE, WOO-BOK</creatorcontrib><creatorcontrib>LEE, HYUN-SOO</creatorcontrib><creatorcontrib>BAE, YONG-SOO</creatorcontrib><creatorcontrib>ONJI, MORIKAZU</creatorcontrib><title>Phase I/II study of immunotherapy using tumor antigen-pulsed dendritic cells in patients with hepatocellular carcinoma</title><title>International journal of oncology</title><addtitle>Int J Oncol</addtitle><description>Dendritic cells (DCs) are increasingly used as adjuvants for vaccination strategies; however, there has been very little development in DC vaccines for patients with hepatocellular carcinoma (HCC). In this study, we assessed the safety, feasibility and efficacy of a multiple tumor-associated antigen (TAA)-pulsed DC vaccine in 5 patients with advanced HCC. DCs were generated by culturing blood monocytes in the presence of granulocyte macrophage-colony stimulating factor and interleukin-4 for 5 days. The DC vaccine was prepared by pulsing DCs with cytoplasmic transduction peptide-attached α-fetoprotein, glypican-3 and MAGE-1 recombinant fusion proteins and cultivating them in the presence of maturation cocktail. DCs were injected subcutaneously near the inguinal lymph nodes, followed by topical application of toll-like receptor-7 agonist around the injection site. We showed that our DC vaccine was safe and well-tolerated over 6 vaccinations in 5 patients. All 5 patients showed T cell responses against TAAs. Clinical benefit was observed in one of the 5 patients. In conclusion, the feasibility, safety and immune activity of DCs pulsed with TAAs were confirmed in HCC patients. However, clinical response was detected only in one patient. Future trials may consider applying this therapy in a less advanced stage to obtain better clinical responses.</description><subject>Aged</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Biological and medical sciences</subject><subject>Cancer Vaccines - adverse effects</subject><subject>Cancer Vaccines - immunology</subject><subject>Cancer Vaccines - therapeutic use</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - therapy</subject><subject>clinical trial</subject><subject>Cytokines - biosynthesis</subject><subject>Cytokines - immunology</subject><subject>dendritic cells</subject><subject>Dendritic Cells - immunology</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Good Manufacturing Practice</subject><subject>hepatocellular carcinoma</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - therapy</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Rodents</subject><subject>T cell receptors</subject><subject>T-Lymphocytes - immunology</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Vaccines</subject><issn>1019-6439</issn><issn>1791-2423</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpVkc-L1DAYhoso7g89epWAiKfM5ksyTXsRZNF1YEEPeg5pkk4ztElN0pX5702ZcVdP-cL38H4vPFX1BsiGNS29cYewoQToBmpaP6suQbSAKafseZkJtLjmrL2orlI6EEK3WwIvqwtKWwG1aC-rh--DShbtbnY7lPJijij0yE3T4kMebFTzES3J-T3KyxQiUj67vfV4XsZkDTLWm-iy00jbcUzIeTSr7KzPCf12eUCDLf-wLpdRRaRV1M6HSb2qXvSqRLw-v9fVzy-ff9x-xfff7na3n-6x5kJkzLgllBPC6gZMB1yDtZ3eWgtCW9ILK2ohmr4GCz3pOtUrTRtjSc2p4Yw37Lr6eMqdl26yRpdmUY1yjm5S8SiDcvL_jXeD3IcHybYNawQtAe_OATH8WmzK8hCW6EtnCS2jjFJooVD4ROkYUoq2f7wARK6aZNEkV01y1VT4t__WeqT_einA-zOgklZjH5XXLj1xRSphZK334cSlWXnjTHhiykXMAZMthpoA-wPW8Ks9</recordid><startdate>20121101</startdate><enddate>20121101</enddate><creator>TADA, FUJIMASA</creator><creator>ABE, MASANORI</creator><creator>HIROOKA, MASASHI</creator><creator>IKEDA, YOSHIOU</creator><creator>HIASA, YOICHI</creator><creator>LEE, YOON</creator><creator>JUNG, NAM-CHUL</creator><creator>LEE, WOO-BOK</creator><creator>LEE, HYUN-SOO</creator><creator>BAE, YONG-SOO</creator><creator>ONJI, MORIKAZU</creator><general>D.A. Spandidos</general><general>Editorial Academy of the International Journal of Oncology</general><general>Spandidos Publications UK Ltd</general><scope>IQODW</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20121101</creationdate><title>Phase I/II study of immunotherapy using tumor antigen-pulsed dendritic cells in patients with hepatocellular carcinoma</title><author>TADA, FUJIMASA ; ABE, MASANORI ; HIROOKA, MASASHI ; IKEDA, YOSHIOU ; HIASA, YOICHI ; LEE, YOON ; JUNG, NAM-CHUL ; LEE, WOO-BOK ; LEE, HYUN-SOO ; BAE, YONG-SOO ; ONJI, MORIKAZU</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-34e024003681db14c1eebc5ee17ce0f7e76778f61e1f0bbafac28de0642d43483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aged</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Biological and medical sciences</topic><topic>Cancer Vaccines - adverse effects</topic><topic>Cancer Vaccines - immunology</topic><topic>Cancer Vaccines - therapeutic use</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - therapy</topic><topic>clinical trial</topic><topic>Cytokines - biosynthesis</topic><topic>Cytokines - immunology</topic><topic>dendritic cells</topic><topic>Dendritic Cells - immunology</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Good Manufacturing Practice</topic><topic>hepatocellular carcinoma</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - therapy</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Rodents</topic><topic>T cell receptors</topic><topic>T-Lymphocytes - immunology</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>TADA, FUJIMASA</creatorcontrib><creatorcontrib>ABE, MASANORI</creatorcontrib><creatorcontrib>HIROOKA, MASASHI</creatorcontrib><creatorcontrib>IKEDA, YOSHIOU</creatorcontrib><creatorcontrib>HIASA, YOICHI</creatorcontrib><creatorcontrib>LEE, YOON</creatorcontrib><creatorcontrib>JUNG, NAM-CHUL</creatorcontrib><creatorcontrib>LEE, WOO-BOK</creatorcontrib><creatorcontrib>LEE, HYUN-SOO</creatorcontrib><creatorcontrib>BAE, YONG-SOO</creatorcontrib><creatorcontrib>ONJI, MORIKAZU</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>TADA, FUJIMASA</au><au>ABE, MASANORI</au><au>HIROOKA, MASASHI</au><au>IKEDA, YOSHIOU</au><au>HIASA, YOICHI</au><au>LEE, YOON</au><au>JUNG, NAM-CHUL</au><au>LEE, WOO-BOK</au><au>LEE, HYUN-SOO</au><au>BAE, YONG-SOO</au><au>ONJI, MORIKAZU</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase I/II study of immunotherapy using tumor antigen-pulsed dendritic cells in patients with hepatocellular carcinoma</atitle><jtitle>International journal of oncology</jtitle><addtitle>Int J Oncol</addtitle><date>2012-11-01</date><risdate>2012</risdate><volume>41</volume><issue>5</issue><spage>1601</spage><epage>1609</epage><pages>1601-1609</pages><issn>1019-6439</issn><eissn>1791-2423</eissn><abstract>Dendritic cells (DCs) are increasingly used as adjuvants for vaccination strategies; however, there has been very little development in DC vaccines for patients with hepatocellular carcinoma (HCC). In this study, we assessed the safety, feasibility and efficacy of a multiple tumor-associated antigen (TAA)-pulsed DC vaccine in 5 patients with advanced HCC. DCs were generated by culturing blood monocytes in the presence of granulocyte macrophage-colony stimulating factor and interleukin-4 for 5 days. The DC vaccine was prepared by pulsing DCs with cytoplasmic transduction peptide-attached α-fetoprotein, glypican-3 and MAGE-1 recombinant fusion proteins and cultivating them in the presence of maturation cocktail. DCs were injected subcutaneously near the inguinal lymph nodes, followed by topical application of toll-like receptor-7 agonist around the injection site. We showed that our DC vaccine was safe and well-tolerated over 6 vaccinations in 5 patients. All 5 patients showed T cell responses against TAAs. Clinical benefit was observed in one of the 5 patients. In conclusion, the feasibility, safety and immune activity of DCs pulsed with TAAs were confirmed in HCC patients. However, clinical response was detected only in one patient. Future trials may consider applying this therapy in a less advanced stage to obtain better clinical responses.</abstract><cop>Athens</cop><pub>D.A. Spandidos</pub><pmid>22971679</pmid><doi>10.3892/ijo.2012.1626</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of oncology, 2012-11, Vol.41 (5), p.1601-1609 |
| issn | 1019-6439 1791-2423 |
| language | eng |
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| source | Spandidos Publications Journals; MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Aged Antigens, Neoplasm - immunology Biological and medical sciences Cancer Vaccines - adverse effects Cancer Vaccines - immunology Cancer Vaccines - therapeutic use Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - therapy clinical trial Cytokines - biosynthesis Cytokines - immunology dendritic cells Dendritic Cells - immunology Female Gastroenterology. Liver. Pancreas. Abdomen Good Manufacturing Practice hepatocellular carcinoma Humans Immunotherapy Liver cancer Liver Neoplasms - pathology Liver Neoplasms - therapy Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Middle Aged Neoplasm Staging Rodents T cell receptors T-Lymphocytes - immunology Treatment Outcome Tumors Vaccines |
| title | Phase I/II study of immunotherapy using tumor antigen-pulsed dendritic cells in patients with hepatocellular carcinoma |
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