TRAIL gene-armed oncolytic poxvirus and oxaliplatin can work synergistically against colorectal cancer
We have explored a unique combination therapy for metastatic colorectal cancer. This strategy combines a potent and new oncolytic poxvirus expressing a membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or TNFSF10) and oxaliplatin (Ox) chemotherapy. We hypothesized that TR...
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| Veröffentlicht in: | Gene therapy 2010-04, Vol.17 (4), p.550-559 |
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| creator | Ziauddin, M F Guo, Z S O'Malley, M E Austin, F Popovic, P J Kavanagh, M A Li, J Sathaiah, M Thirunavukarasu, P Fang, B Lee, Y J Bartlett, D L |
| description | We have explored a unique combination therapy for metastatic colorectal cancer. This strategy combines a potent and new oncolytic poxvirus expressing a membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or TNFSF10) and oxaliplatin (Ox) chemotherapy. We hypothesized that TRAIL expression would increase the efficacy of the oncolytic poxvirus, and that the therapeutic efficacy would be further enhanced by combination with chemotherapy. The cytotoxicity to cancer cells by Ox, oncolytic vaccinia virus (VV) and
trail
gene-armed VV alone or in combination was tested
in vitro
. The
trail
gene armed oncolytic VV-expressed high levels of TRAIL in infected cancer cells and had greater potency as a cytotoxic agent compared with the parent VV. Ox alone exerted concentration-dependent cytotoxicity.
In vitro
, the combination of the two agents applied at suboptimal concentrations for individual therapy displayed synergy in inducing cancer cells into enhanced levels of apoptosis/necrosis. Western blot analyses were consistent with the notion that TRAIL induced cancer cell death mainly through apoptosis, whereas Ox and vJS6 induced cell death more through non-apoptotic death pathways. In two aggressive colorectal carcinomatosis models derived from human HCT116 and murine MC38 cells, the combination therapy displayed synergistic or additive antitumor activity and prolonged the survival of the tumor-bearing mice compared with either Ox chemotherapy or vvTRAIL-mediated oncolytic gene therapy alone. This combination strategy may provide a new avenue to treating peritoneal carcinomatosis and other types of metastases of colorectal cancer. |
| doi_str_mv | 10.1038/gt.2010.5 |
| format | Article |
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trail
gene-armed VV alone or in combination was tested
in vitro
. The
trail
gene armed oncolytic VV-expressed high levels of TRAIL in infected cancer cells and had greater potency as a cytotoxic agent compared with the parent VV. Ox alone exerted concentration-dependent cytotoxicity.
In vitro
, the combination of the two agents applied at suboptimal concentrations for individual therapy displayed synergy in inducing cancer cells into enhanced levels of apoptosis/necrosis. Western blot analyses were consistent with the notion that TRAIL induced cancer cell death mainly through apoptosis, whereas Ox and vJS6 induced cell death more through non-apoptotic death pathways. In two aggressive colorectal carcinomatosis models derived from human HCT116 and murine MC38 cells, the combination therapy displayed synergistic or additive antitumor activity and prolonged the survival of the tumor-bearing mice compared with either Ox chemotherapy or vvTRAIL-mediated oncolytic gene therapy alone. This combination strategy may provide a new avenue to treating peritoneal carcinomatosis and other types of metastases of colorectal cancer.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/gt.2010.5</identifier><identifier>PMID: 20182517</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/61/201 ; 631/67/1059/99 ; 631/67/1504/1885 ; 692/700/565/1331 ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Antineoplastic Agents - therapeutic use ; Antitumor activity ; Apoptosis ; Apoptosis - genetics ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Blotting, Western ; Cancer ; Carcinoma - drug therapy ; Carcinoma - genetics ; Carcinoma - therapy ; Care and treatment ; Cell Biology ; Cell death ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Chemotherapy ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - therapy ; Cytotoxicity ; Development and progression ; Flow Cytometry ; Fundamental and applied biological sciences. Psychology ; Gastric cancer ; Gene Expression ; Gene Therapy ; Genetic aspects ; Genetic Therapy - methods ; Health. Pharmaceutical industry ; Human Genetics ; Humans ; Industrial applications and implications. Economical aspects ; Medical sciences ; Metastases ; Metastasis ; Methods ; Mice ; Nanotechnology ; Oncolysis ; Organoplatinum Compounds - therapeutic use ; original-article ; Oxaliplatin ; Physiological aspects ; Poxviridae ; Poxvirus ; TNF-Related Apoptosis-Inducing Ligand - genetics ; TRAIL protein ; Transfection ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Vaccinia virus ; Viruses</subject><ispartof>Gene therapy, 2010-04, Vol.17 (4), p.550-559</ispartof><rights>Macmillan Publishers Limited 2010</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 2010</rights><rights>Macmillan Publishers Limited 2010.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c724t-a5d3cb57f8b7565af154ef264d3b1375055594e4e399b135c5891cfb2e2c75ab3</citedby><cites>FETCH-LOGICAL-c724t-a5d3cb57f8b7565af154ef264d3b1375055594e4e399b135c5891cfb2e2c75ab3</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/gt.2010.5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/gt.2010.5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22561516$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20182517$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ziauddin, M F</creatorcontrib><creatorcontrib>Guo, Z S</creatorcontrib><creatorcontrib>O'Malley, M E</creatorcontrib><creatorcontrib>Austin, F</creatorcontrib><creatorcontrib>Popovic, P J</creatorcontrib><creatorcontrib>Kavanagh, M A</creatorcontrib><creatorcontrib>Li, J</creatorcontrib><creatorcontrib>Sathaiah, M</creatorcontrib><creatorcontrib>Thirunavukarasu, P</creatorcontrib><creatorcontrib>Fang, B</creatorcontrib><creatorcontrib>Lee, Y J</creatorcontrib><creatorcontrib>Bartlett, D L</creatorcontrib><title>TRAIL gene-armed oncolytic poxvirus and oxaliplatin can work synergistically against colorectal cancer</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><addtitle>Gene Ther</addtitle><description>We have explored a unique combination therapy for metastatic colorectal cancer. This strategy combines a potent and new oncolytic poxvirus expressing a membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or TNFSF10) and oxaliplatin (Ox) chemotherapy. We hypothesized that TRAIL expression would increase the efficacy of the oncolytic poxvirus, and that the therapeutic efficacy would be further enhanced by combination with chemotherapy. The cytotoxicity to cancer cells by Ox, oncolytic vaccinia virus (VV) and
trail
gene-armed VV alone or in combination was tested
in vitro
. The
trail
gene armed oncolytic VV-expressed high levels of TRAIL in infected cancer cells and had greater potency as a cytotoxic agent compared with the parent VV. Ox alone exerted concentration-dependent cytotoxicity.
In vitro
, the combination of the two agents applied at suboptimal concentrations for individual therapy displayed synergy in inducing cancer cells into enhanced levels of apoptosis/necrosis. Western blot analyses were consistent with the notion that TRAIL induced cancer cell death mainly through apoptosis, whereas Ox and vJS6 induced cell death more through non-apoptotic death pathways. In two aggressive colorectal carcinomatosis models derived from human HCT116 and murine MC38 cells, the combination therapy displayed synergistic or additive antitumor activity and prolonged the survival of the tumor-bearing mice compared with either Ox chemotherapy or vvTRAIL-mediated oncolytic gene therapy alone. This combination strategy may provide a new avenue to treating peritoneal carcinomatosis and other types of metastases of colorectal cancer.</description><subject>631/61/201</subject><subject>631/67/1059/99</subject><subject>631/67/1504/1885</subject><subject>692/700/565/1331</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Apoptosis - genetics</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>Blotting, Western</subject><subject>Cancer</subject><subject>Carcinoma - drug therapy</subject><subject>Carcinoma - genetics</subject><subject>Carcinoma - therapy</subject><subject>Care and treatment</subject><subject>Cell Biology</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemotherapy</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - therapy</subject><subject>Cytotoxicity</subject><subject>Development and progression</subject><subject>Flow Cytometry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastric cancer</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Genetic aspects</subject><subject>Genetic Therapy - methods</subject><subject>Health. Pharmaceutical industry</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Medical sciences</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Methods</subject><subject>Mice</subject><subject>Nanotechnology</subject><subject>Oncolysis</subject><subject>Organoplatinum Compounds - therapeutic use</subject><subject>original-article</subject><subject>Oxaliplatin</subject><subject>Physiological aspects</subject><subject>Poxviridae</subject><subject>Poxvirus</subject><subject>TNF-Related Apoptosis-Inducing Ligand - genetics</subject><subject>TRAIL protein</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>Antineoplastic Agents - therapeutic use</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>Apoptosis - genetics</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>Blotting, Western</topic><topic>Cancer</topic><topic>Carcinoma - drug therapy</topic><topic>Carcinoma - genetics</topic><topic>Carcinoma - therapy</topic><topic>Care and treatment</topic><topic>Cell Biology</topic><topic>Cell death</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Chemotherapy</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - therapy</topic><topic>Cytotoxicity</topic><topic>Development and progression</topic><topic>Flow Cytometry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastric cancer</topic><topic>Gene Expression</topic><topic>Gene Therapy</topic><topic>Genetic aspects</topic><topic>Genetic Therapy - methods</topic><topic>Health. Pharmaceutical industry</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Medical sciences</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Methods</topic><topic>Mice</topic><topic>Nanotechnology</topic><topic>Oncolysis</topic><topic>Organoplatinum Compounds - therapeutic use</topic><topic>original-article</topic><topic>Oxaliplatin</topic><topic>Physiological aspects</topic><topic>Poxviridae</topic><topic>Poxvirus</topic><topic>TNF-Related Apoptosis-Inducing Ligand - genetics</topic><topic>TRAIL protein</topic><topic>Transfection</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><topic>Vaccinia virus</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ziauddin, M F</creatorcontrib><creatorcontrib>Guo, Z S</creatorcontrib><creatorcontrib>O'Malley, M E</creatorcontrib><creatorcontrib>Austin, F</creatorcontrib><creatorcontrib>Popovic, P J</creatorcontrib><creatorcontrib>Kavanagh, M A</creatorcontrib><creatorcontrib>Li, J</creatorcontrib><creatorcontrib>Sathaiah, M</creatorcontrib><creatorcontrib>Thirunavukarasu, P</creatorcontrib><creatorcontrib>Fang, B</creatorcontrib><creatorcontrib>Lee, Y J</creatorcontrib><creatorcontrib>Bartlett, D L</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>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ziauddin, M F</au><au>Guo, Z S</au><au>O'Malley, M E</au><au>Austin, F</au><au>Popovic, P J</au><au>Kavanagh, M A</au><au>Li, J</au><au>Sathaiah, M</au><au>Thirunavukarasu, P</au><au>Fang, B</au><au>Lee, Y J</au><au>Bartlett, D L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TRAIL gene-armed oncolytic poxvirus and oxaliplatin can work synergistically against colorectal cancer</atitle><jtitle>Gene therapy</jtitle><stitle>Gene Ther</stitle><addtitle>Gene Ther</addtitle><date>2010-04-01</date><risdate>2010</risdate><volume>17</volume><issue>4</issue><spage>550</spage><epage>559</epage><pages>550-559</pages><issn>0969-7128</issn><eissn>1476-5462</eissn><abstract>We have explored a unique combination therapy for metastatic colorectal cancer. This strategy combines a potent and new oncolytic poxvirus expressing a membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or TNFSF10) and oxaliplatin (Ox) chemotherapy. We hypothesized that TRAIL expression would increase the efficacy of the oncolytic poxvirus, and that the therapeutic efficacy would be further enhanced by combination with chemotherapy. The cytotoxicity to cancer cells by Ox, oncolytic vaccinia virus (VV) and
trail
gene-armed VV alone or in combination was tested
in vitro
. The
trail
gene armed oncolytic VV-expressed high levels of TRAIL in infected cancer cells and had greater potency as a cytotoxic agent compared with the parent VV. Ox alone exerted concentration-dependent cytotoxicity.
In vitro
, the combination of the two agents applied at suboptimal concentrations for individual therapy displayed synergy in inducing cancer cells into enhanced levels of apoptosis/necrosis. Western blot analyses were consistent with the notion that TRAIL induced cancer cell death mainly through apoptosis, whereas Ox and vJS6 induced cell death more through non-apoptotic death pathways. In two aggressive colorectal carcinomatosis models derived from human HCT116 and murine MC38 cells, the combination therapy displayed synergistic or additive antitumor activity and prolonged the survival of the tumor-bearing mice compared with either Ox chemotherapy or vvTRAIL-mediated oncolytic gene therapy alone. This combination strategy may provide a new avenue to treating peritoneal carcinomatosis and other types of metastases of colorectal cancer.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20182517</pmid><doi>10.1038/gt.2010.5</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0969-7128 |
| ispartof | Gene therapy, 2010-04, Vol.17 (4), p.550-559 |
| issn | 0969-7128 1476-5462 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3250063 |
| source | MEDLINE; SpringerLink Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | 631/61/201 631/67/1059/99 631/67/1504/1885 692/700/565/1331 Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Antineoplastic Agents - therapeutic use Antitumor activity Apoptosis Apoptosis - genetics Applied cell therapy and gene therapy Biological and medical sciences Biomedical and Life Sciences Biomedicine Biotechnology Blotting, Western Cancer Carcinoma - drug therapy Carcinoma - genetics Carcinoma - therapy Care and treatment Cell Biology Cell death Cell Line, Tumor Cell Proliferation - drug effects Chemotherapy Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Colorectal Neoplasms - therapy Cytotoxicity Development and progression Flow Cytometry Fundamental and applied biological sciences. Psychology Gastric cancer Gene Expression Gene Therapy Genetic aspects Genetic Therapy - methods Health. Pharmaceutical industry Human Genetics Humans Industrial applications and implications. Economical aspects Medical sciences Metastases Metastasis Methods Mice Nanotechnology Oncolysis Organoplatinum Compounds - therapeutic use original-article Oxaliplatin Physiological aspects Poxviridae Poxvirus TNF-Related Apoptosis-Inducing Ligand - genetics TRAIL protein Transfection Transfusions. Complications. Transfusion reactions. Cell and gene therapy Vaccinia virus Viruses |
| title | TRAIL gene-armed oncolytic poxvirus and oxaliplatin can work synergistically against colorectal cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T13%3A15%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=TRAIL%20gene-armed%20oncolytic%20poxvirus%20and%20oxaliplatin%20can%20work%20synergistically%20against%20colorectal%20cancer&rft.jtitle=Gene%20therapy&rft.au=Ziauddin,%20M%20F&rft.date=2010-04-01&rft.volume=17&rft.issue=4&rft.spage=550&rft.epage=559&rft.pages=550-559&rft.issn=0969-7128&rft.eissn=1476-5462&rft_id=info:doi/10.1038/gt.2010.5&rft_dat=%3Cgale_pubme%3EA224168247%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=218719515&rft_id=info:pmid/20182517&rft_galeid=A224168247&rfr_iscdi=true |