Injection of IL-12 gene-transduced dendritic cells into mouse liver tumor lesions activates both innate and acquired immunity
Dendritic cell (DC)-based vaccines have been applied clinically in the setting of advanced-stage cancer. To date, the clinical efficacy of these vaccines has been limited, possibly owing to the impairment of transferred DC function in cancer-bearing patients. In this study, we examined the therapeut...
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| Veröffentlicht in: | Gene therapy 2007-06, Vol.14 (11), p.863-871 |
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| creator | Tatsumi, T Takehara, T Yamaguchi, S Sasakawa, A Miyagi, T Jinushi, M Sakamori, R Kohga, K Uemura, A Ohkawa, K Storkus, W J Hayashi, N |
| description | Dendritic cell (DC)-based vaccines have been applied clinically in the setting of advanced-stage cancer. To date, the clinical efficacy of these vaccines has been limited, possibly owing to the impairment of transferred DC function in cancer-bearing patients. In this study, we examined the therapeutic efficacy of interleukin-12 (IL-12) gene-transfected DCs isolated from tumor-bearing hosts against liver tumor. The endogenous DCs isolated from subcutaneous (s.c.) CMS4 tumor-bearing mice (CMS4DC) exhibited decreased expression levels of antigen-presenting molecules and low-allostimulatory capacity. CMS4DC produced less IL-12p70 than DCs isolated from normal mice. Adenoviral transfection of IL-12 gene into CMS4DC (AdIL12DC) restored the expression of antigen-presenting molecules and allostimulatory capacity. Intratumoral (i.t.) delivery of AdIL12DC resulted in complete rejection of intrahepatic CMS4 tumors and activation of innate and acquired immune cells. Antibody depletion studies revealed that both CD4
+
and CD8
+
T cells as well as natural killer cells play critical roles in mediating liver tumor rejection. I.t. treatment of AdIL12DC resulted in long-term protection against s.c. rechallenge with CMS4 tumor cells. These results revealed that IL-12 gene transfer is capable of improving the impaired functions of DC isolated from tumor-bearing hosts, and support the preclinical therapeutic efficacy of intrahepatic injection of AdIL12DC. |
| doi_str_mv | 10.1038/sj.gt.3302941 |
| format | Article |
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+
and CD8
+
T cells as well as natural killer cells play critical roles in mediating liver tumor rejection. I.t. treatment of AdIL12DC resulted in long-term protection against s.c. rechallenge with CMS4 tumor cells. These results revealed that IL-12 gene transfer is capable of improving the impaired functions of DC isolated from tumor-bearing hosts, and support the preclinical therapeutic efficacy of intrahepatic injection of AdIL12DC.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/sj.gt.3302941</identifier><identifier>PMID: 17344900</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adenoviridae - genetics ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Antigens ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Cancer Vaccines - administration & dosage ; Cancer Vaccines - immunology ; Care and treatment ; CD4 antigen ; CD8 antigen ; Cell Biology ; Cytotoxicity Tests, Immunologic - methods ; Dendritic cells ; Dendritic Cells - immunology ; Female ; Flow Cytometry ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene Therapy ; Gene transfer ; Genetic aspects ; Genetic Therapy - methods ; Genetic Vectors - administration & dosage ; Genetic Vectors - genetics ; Health aspects ; Health. Pharmaceutical industry ; Hepatocytes ; Human Genetics ; Immunity ; Immunology ; Immunotherapy, Adoptive - methods ; Industrial applications and implications. Economical aspects ; Injection ; Injections, Intralesional ; Interleukin 12 ; Interleukin-12 - genetics ; Interleukin-12 - immunology ; Killer Cells, Natural - immunology ; Liver ; Liver cancer ; Liver Neoplasms - immunology ; Liver Neoplasms - prevention & control ; Liver Neoplasms - therapy ; Liver tumors ; Lymphocyte Activation ; Lymphocytes T ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Nanotechnology ; Natural killer cells ; Neoplasms, Experimental ; original-article ; Rodents ; T-Lymphocytes, Cytotoxic - immunology ; Time Factors ; Transduction, Genetic - methods ; Transfection ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Tumor cells ; Tumors ; Vaccines</subject><ispartof>Gene therapy, 2007-06, Vol.14 (11), p.863-871</ispartof><rights>Springer Nature Limited 2007</rights><rights>2007 INIST-CNRS</rights><rights>COPYRIGHT 2007 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2007</rights><rights>Nature Publishing Group 2007.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c617t-7bd03524b3b0a51df2d59faa953fdf7c44945db9e24fc8662a7b681ab0fb64de3</citedby><cites>FETCH-LOGICAL-c617t-7bd03524b3b0a51df2d59faa953fdf7c44945db9e24fc8662a7b681ab0fb64de3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.gt.3302941$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.gt.3302941$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18735583$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17344900$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tatsumi, T</creatorcontrib><creatorcontrib>Takehara, T</creatorcontrib><creatorcontrib>Yamaguchi, S</creatorcontrib><creatorcontrib>Sasakawa, A</creatorcontrib><creatorcontrib>Miyagi, T</creatorcontrib><creatorcontrib>Jinushi, M</creatorcontrib><creatorcontrib>Sakamori, R</creatorcontrib><creatorcontrib>Kohga, K</creatorcontrib><creatorcontrib>Uemura, A</creatorcontrib><creatorcontrib>Ohkawa, K</creatorcontrib><creatorcontrib>Storkus, W J</creatorcontrib><creatorcontrib>Hayashi, N</creatorcontrib><title>Injection of IL-12 gene-transduced dendritic cells into mouse liver tumor lesions activates both innate and acquired immunity</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><addtitle>Gene Ther</addtitle><description>Dendritic cell (DC)-based vaccines have been applied clinically in the setting of advanced-stage cancer. To date, the clinical efficacy of these vaccines has been limited, possibly owing to the impairment of transferred DC function in cancer-bearing patients. In this study, we examined the therapeutic efficacy of interleukin-12 (IL-12) gene-transfected DCs isolated from tumor-bearing hosts against liver tumor. The endogenous DCs isolated from subcutaneous (s.c.) CMS4 tumor-bearing mice (CMS4DC) exhibited decreased expression levels of antigen-presenting molecules and low-allostimulatory capacity. CMS4DC produced less IL-12p70 than DCs isolated from normal mice. Adenoviral transfection of IL-12 gene into CMS4DC (AdIL12DC) restored the expression of antigen-presenting molecules and allostimulatory capacity. Intratumoral (i.t.) delivery of AdIL12DC resulted in complete rejection of intrahepatic CMS4 tumors and activation of innate and acquired immune cells. Antibody depletion studies revealed that both CD4
+
and CD8
+
T cells as well as natural killer cells play critical roles in mediating liver tumor rejection. I.t. treatment of AdIL12DC resulted in long-term protection against s.c. rechallenge with CMS4 tumor cells. These results revealed that IL-12 gene transfer is capable of improving the impaired functions of DC isolated from tumor-bearing hosts, and support the preclinical therapeutic efficacy of intrahepatic injection of AdIL12DC.</description><subject>Adenoviridae - genetics</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Antigens</subject><subject>Applied cell therapy and gene therapy</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Cancer Vaccines - administration & dosage</subject><subject>Cancer Vaccines - immunology</subject><subject>Care and treatment</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Cell Biology</subject><subject>Cytotoxicity Tests, Immunologic - methods</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - immunology</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Gene transfer</subject><subject>Genetic aspects</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors - administration & dosage</subject><subject>Genetic Vectors - genetics</subject><subject>Health aspects</subject><subject>Health. Pharmaceutical industry</subject><subject>Hepatocytes</subject><subject>Human Genetics</subject><subject>Immunity</subject><subject>Immunology</subject><subject>Immunotherapy, Adoptive - methods</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Injection</subject><subject>Injections, Intralesional</subject><subject>Interleukin 12</subject><subject>Interleukin-12 - genetics</subject><subject>Interleukin-12 - immunology</subject><subject>Killer Cells, Natural - immunology</subject><subject>Liver</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - immunology</subject><subject>Liver Neoplasms - prevention & control</subject><subject>Liver Neoplasms - therapy</subject><subject>Liver tumors</subject><subject>Lymphocyte Activation</subject><subject>Lymphocytes T</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nanotechnology</subject><subject>Natural killer cells</subject><subject>Neoplasms, Experimental</subject><subject>original-article</subject><subject>Rodents</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Time Factors</subject><subject>Transduction, Genetic - methods</subject><subject>Transfection</subject><subject>Transfusions. Complications. Transfusion reactions. 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Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Antigens</topic><topic>Applied cell therapy and gene therapy</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Cancer Vaccines - administration & dosage</topic><topic>Cancer Vaccines - immunology</topic><topic>Care and treatment</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>Cell Biology</topic><topic>Cytotoxicity Tests, Immunologic - methods</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - immunology</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene Therapy</topic><topic>Gene transfer</topic><topic>Genetic aspects</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors - administration & dosage</topic><topic>Genetic Vectors - genetics</topic><topic>Health aspects</topic><topic>Health. Pharmaceutical industry</topic><topic>Hepatocytes</topic><topic>Human Genetics</topic><topic>Immunity</topic><topic>Immunology</topic><topic>Immunotherapy, Adoptive - methods</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Injection</topic><topic>Injections, Intralesional</topic><topic>Interleukin 12</topic><topic>Interleukin-12 - genetics</topic><topic>Interleukin-12 - immunology</topic><topic>Killer Cells, Natural - immunology</topic><topic>Liver</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - immunology</topic><topic>Liver Neoplasms - prevention & control</topic><topic>Liver Neoplasms - therapy</topic><topic>Liver tumors</topic><topic>Lymphocyte Activation</topic><topic>Lymphocytes T</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Nanotechnology</topic><topic>Natural killer cells</topic><topic>Neoplasms, Experimental</topic><topic>original-article</topic><topic>Rodents</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Time Factors</topic><topic>Transduction, Genetic - methods</topic><topic>Transfection</topic><topic>Transfusions. Complications. Transfusion reactions. 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To date, the clinical efficacy of these vaccines has been limited, possibly owing to the impairment of transferred DC function in cancer-bearing patients. In this study, we examined the therapeutic efficacy of interleukin-12 (IL-12) gene-transfected DCs isolated from tumor-bearing hosts against liver tumor. The endogenous DCs isolated from subcutaneous (s.c.) CMS4 tumor-bearing mice (CMS4DC) exhibited decreased expression levels of antigen-presenting molecules and low-allostimulatory capacity. CMS4DC produced less IL-12p70 than DCs isolated from normal mice. Adenoviral transfection of IL-12 gene into CMS4DC (AdIL12DC) restored the expression of antigen-presenting molecules and allostimulatory capacity. Intratumoral (i.t.) delivery of AdIL12DC resulted in complete rejection of intrahepatic CMS4 tumors and activation of innate and acquired immune cells. Antibody depletion studies revealed that both CD4
+
and CD8
+
T cells as well as natural killer cells play critical roles in mediating liver tumor rejection. I.t. treatment of AdIL12DC resulted in long-term protection against s.c. rechallenge with CMS4 tumor cells. These results revealed that IL-12 gene transfer is capable of improving the impaired functions of DC isolated from tumor-bearing hosts, and support the preclinical therapeutic efficacy of intrahepatic injection of AdIL12DC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>17344900</pmid><doi>10.1038/sj.gt.3302941</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0969-7128 |
| ispartof | Gene therapy, 2007-06, Vol.14 (11), p.863-871 |
| issn | 0969-7128 1476-5462 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_19863200 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SpringerLink Journals - AutoHoldings |
| subjects | Adenoviridae - genetics Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Antigens Applied cell therapy and gene therapy Biological and medical sciences Biomedical and Life Sciences Biomedicine Biotechnology Cancer Vaccines - administration & dosage Cancer Vaccines - immunology Care and treatment CD4 antigen CD8 antigen Cell Biology Cytotoxicity Tests, Immunologic - methods Dendritic cells Dendritic Cells - immunology Female Flow Cytometry Fundamental and applied biological sciences. Psychology Gene Expression Gene Therapy Gene transfer Genetic aspects Genetic Therapy - methods Genetic Vectors - administration & dosage Genetic Vectors - genetics Health aspects Health. Pharmaceutical industry Hepatocytes Human Genetics Immunity Immunology Immunotherapy, Adoptive - methods Industrial applications and implications. Economical aspects Injection Injections, Intralesional Interleukin 12 Interleukin-12 - genetics Interleukin-12 - immunology Killer Cells, Natural - immunology Liver Liver cancer Liver Neoplasms - immunology Liver Neoplasms - prevention & control Liver Neoplasms - therapy Liver tumors Lymphocyte Activation Lymphocytes T Medical sciences Mice Mice, Inbred BALB C Nanotechnology Natural killer cells Neoplasms, Experimental original-article Rodents T-Lymphocytes, Cytotoxic - immunology Time Factors Transduction, Genetic - methods Transfection Transfusions. Complications. Transfusion reactions. Cell and gene therapy Tumor cells Tumors Vaccines |
| title | Injection of IL-12 gene-transduced dendritic cells into mouse liver tumor lesions activates both innate and acquired immunity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T19%3A49%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Injection%20of%20IL-12%20gene-transduced%20dendritic%20cells%20into%20mouse%20liver%20tumor%20lesions%20activates%20both%20innate%20and%20acquired%20immunity&rft.jtitle=Gene%20therapy&rft.au=Tatsumi,%20T&rft.date=2007-06-01&rft.volume=14&rft.issue=11&rft.spage=863&rft.epage=871&rft.pages=863-871&rft.issn=0969-7128&rft.eissn=1476-5462&rft_id=info:doi/10.1038/sj.gt.3302941&rft_dat=%3Cgale_proqu%3EA181763482%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=218722128&rft_id=info:pmid/17344900&rft_galeid=A181763482&rfr_iscdi=true |