Dynamics of melanoma tumor therapy with vesicular stomatitis virus: explaining the variability in outcomes using mathematical modeling
Tumor selective, replication competent viruses are being tested for cancer gene therapy. This approach introduces a new therapeutic paradigm due to potential replication of the therapeutic agent and induction of a tumor-specific immune response. However, the experimental outcomes are quite variable,...
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| Veröffentlicht in: | Gene therapy 2012-05, Vol.19 (5), p.543-549 |
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| creator | Rommelfanger, D M Offord, C P Dev, J Bajzer, Z Vile, R G Dingli, D |
| description | Tumor selective, replication competent viruses are being tested for cancer gene therapy. This approach introduces a new therapeutic paradigm due to potential replication of the therapeutic agent and induction of a tumor-specific immune response. However, the experimental outcomes are quite variable, even when studies utilize highly inbred strains of mice and the same cell line and virus. Recognizing that virotherapy is an exercise in population dynamics, we utilize mathematical modeling to understand the variable outcomes observed when B16ova malignant melanoma tumors are treated with vesicular stomatitis virus in syngeneic, fully immunocompetent mice. We show how variability in the initial tumor size and the actual amount of virus delivered to the tumor have critical roles on the outcome of therapy. Virotherapy works best when tumors are small, and a robust innate immune response can lead to superior tumor control. Strategies that reduce tumor burden without suppressing the immune response and methods that maximize the amount of virus delivered to the tumor should optimize tumor control in this model system. |
| doi_str_mv | 10.1038/gt.2011.132 |
| format | Article |
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This approach introduces a new therapeutic paradigm due to potential replication of the therapeutic agent and induction of a tumor-specific immune response. However, the experimental outcomes are quite variable, even when studies utilize highly inbred strains of mice and the same cell line and virus. Recognizing that virotherapy is an exercise in population dynamics, we utilize mathematical modeling to understand the variable outcomes observed when B16ova malignant melanoma tumors are treated with vesicular stomatitis virus in syngeneic, fully immunocompetent mice. We show how variability in the initial tumor size and the actual amount of virus delivered to the tumor have critical roles on the outcome of therapy. Virotherapy works best when tumors are small, and a robust innate immune response can lead to superior tumor control. Strategies that reduce tumor burden without suppressing the immune response and methods that maximize the amount of virus delivered to the tumor should optimize tumor control in this model system.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/gt.2011.132</identifier><identifier>PMID: 21918546</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animal models ; Animals ; Antimitotic agents ; Antineoplastic agents ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Cancer ; Cancer therapies ; Cell Biology ; Cell Line, Tumor ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Diagnosis ; Drug therapy ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene Therapy ; Genetic aspects ; Health aspects ; Health. Pharmaceutical industry ; Human Genetics ; Immune response ; Immunotherapy ; Inbreeding ; Industrial applications and implications. Economical aspects ; Innate immunity ; Mathematical models ; Mathematics ; Medical sciences ; Melanoma ; Melanoma, Experimental - therapy ; Mice ; Mice, Inbred C57BL ; Models, Theoretical ; Molecular and cellular biology ; Nanotechnology ; Oncolytic Virotherapy - methods ; original-article ; Physical training ; Population dynamics ; Replication ; Risk factors ; Skin cancer ; Stomatitis ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Tumors ; Vesicular stomatitis Indiana virus - genetics ; Vesicular stomatitis Indiana virus - immunology ; Vesicular stomatitis virus ; Virus Replication ; Viruses</subject><ispartof>Gene therapy, 2012-05, Vol.19 (5), p.543-549</ispartof><rights>Macmillan Publishers Limited 2012</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2012 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 2012</rights><rights>Macmillan Publishers Limited 2012.</rights><rights>2012 Macmillan Publishers Limited All rights reserved 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c669t-73d9fd496efae2fae92647299cce4c9eeca5ef5edf0b3463546594ccae5115813</citedby><cites>FETCH-LOGICAL-c669t-73d9fd496efae2fae92647299cce4c9eeca5ef5edf0b3463546594ccae5115813</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.2011.132$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/gt.2011.132$$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=25855751$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21918546$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rommelfanger, D M</creatorcontrib><creatorcontrib>Offord, C P</creatorcontrib><creatorcontrib>Dev, J</creatorcontrib><creatorcontrib>Bajzer, Z</creatorcontrib><creatorcontrib>Vile, R G</creatorcontrib><creatorcontrib>Dingli, D</creatorcontrib><title>Dynamics of melanoma tumor therapy with vesicular stomatitis virus: explaining the variability in outcomes using mathematical modeling</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><addtitle>Gene Ther</addtitle><description>Tumor selective, replication competent viruses are being tested for cancer gene therapy. This approach introduces a new therapeutic paradigm due to potential replication of the therapeutic agent and induction of a tumor-specific immune response. However, the experimental outcomes are quite variable, even when studies utilize highly inbred strains of mice and the same cell line and virus. Recognizing that virotherapy is an exercise in population dynamics, we utilize mathematical modeling to understand the variable outcomes observed when B16ova malignant melanoma tumors are treated with vesicular stomatitis virus in syngeneic, fully immunocompetent mice. We show how variability in the initial tumor size and the actual amount of virus delivered to the tumor have critical roles on the outcome of therapy. Virotherapy works best when tumors are small, and a robust innate immune response can lead to superior tumor control. Strategies that reduce tumor burden without suppressing the immune response and methods that maximize the amount of virus delivered to the tumor should optimize tumor control in this model system.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antimitotic agents</subject><subject>Antineoplastic agents</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</subject><subject>Cancer therapies</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Diagnosis</subject><subject>Drug therapy</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Health. Pharmaceutical industry</subject><subject>Human Genetics</subject><subject>Immune response</subject><subject>Immunotherapy</subject><subject>Inbreeding</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Innate immunity</subject><subject>Mathematical models</subject><subject>Mathematics</subject><subject>Medical sciences</subject><subject>Melanoma</subject><subject>Melanoma, Experimental - therapy</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Models, Theoretical</subject><subject>Molecular and cellular biology</subject><subject>Nanotechnology</subject><subject>Oncolytic Virotherapy - methods</subject><subject>original-article</subject><subject>Physical training</subject><subject>Population dynamics</subject><subject>Replication</subject><subject>Risk factors</subject><subject>Skin cancer</subject><subject>Stomatitis</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>Tumors</subject><subject>Vesicular stomatitis Indiana virus - genetics</subject><subject>Vesicular stomatitis Indiana virus - immunology</subject><subject>Vesicular stomatitis virus</subject><subject>Virus Replication</subject><subject>Viruses</subject><issn>0969-7128</issn><issn>1476-5462</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNktuKFDEQhhtR3HX0ynsJiKLojJ10-hAvhGU9LSwIHq5DJl3dnaU7mU3S484L-NxWM-PujIpICIHKV39RVX-SPKTpgqZZ9aqNC5ZSuqAZu5UcU14W85wX7HZynIpCzEvKqqPkXggXaZrysmJ3kyNGBa0QOk5-vN1YNRgdiGvIAL2yblAkjoPzJHbg1WpDvpvYkTUEo8deeRIiItFEE8ja-DG8JnC16pWxxrZTDlkrb9TS9CZuiLHEjVG7AQIZw0RgbgeTgFY9GVwNPUbvJ3ca1Qd4sHtnybf3776efpyff_pwdnpyPtdFIeK8zGrR1FwU0ChgeAUreMmE0Bq4FgBa5dDkUDfpMuNFhi3mgmutIKc0r2g2S95sdVfjcoBag41e9XLlzaD8Rjpl5OGPNZ1s3VpmIuNZXqDAs52Ad5cjhCgHEzT0ODhwY5A0paXIRcGq_0FZyQuKS5wlj39DL9zoLU5CYoMcey-r8l8UalGBm8-KG6pVPUhjG4eN6Km0PGEi5bRilCO1-AuFpwZ0g7PQGIwfJDw_SEAmwlVs1RiCPPvy-ZB9usd2oPrYBdeP0TgbDsEXW1B7F4KH5noTNJWTuWUb5WRuieZG-tH-8q7ZX25G4MkOUAHd1XhltQk3XF7leZlPLni55QJ-2Rb8_iD_rPsTSk0QCQ</recordid><startdate>20120501</startdate><enddate>20120501</enddate><creator>Rommelfanger, D M</creator><creator>Offord, C P</creator><creator>Dev, J</creator><creator>Bajzer, Z</creator><creator>Vile, R G</creator><creator>Dingli, D</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>7QO</scope><scope>5PM</scope></search><sort><creationdate>20120501</creationdate><title>Dynamics of melanoma tumor therapy with vesicular stomatitis virus: explaining the variability in outcomes using mathematical modeling</title><author>Rommelfanger, D M ; Offord, C P ; Dev, J ; Bajzer, Z ; Vile, R G ; Dingli, D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c669t-73d9fd496efae2fae92647299cce4c9eeca5ef5edf0b3463546594ccae5115813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antimitotic agents</topic><topic>Antineoplastic agents</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</topic><topic>Cancer therapies</topic><topic>Cell Biology</topic><topic>Cell Line, Tumor</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Diagnosis</topic><topic>Drug therapy</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene Therapy</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Health. 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This approach introduces a new therapeutic paradigm due to potential replication of the therapeutic agent and induction of a tumor-specific immune response. However, the experimental outcomes are quite variable, even when studies utilize highly inbred strains of mice and the same cell line and virus. Recognizing that virotherapy is an exercise in population dynamics, we utilize mathematical modeling to understand the variable outcomes observed when B16ova malignant melanoma tumors are treated with vesicular stomatitis virus in syngeneic, fully immunocompetent mice. We show how variability in the initial tumor size and the actual amount of virus delivered to the tumor have critical roles on the outcome of therapy. Virotherapy works best when tumors are small, and a robust innate immune response can lead to superior tumor control. Strategies that reduce tumor burden without suppressing the immune response and methods that maximize the amount of virus delivered to the tumor should optimize tumor control in this model system.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>21918546</pmid><doi>10.1038/gt.2011.132</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Gene therapy, 2012-05, Vol.19 (5), p.543-549 |
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| language | eng |
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| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animal models Animals Antimitotic agents Antineoplastic agents Applied cell therapy and gene therapy Biological and medical sciences Biomedical and Life Sciences Biomedicine Biotechnology Cancer Cancer therapies Cell Biology Cell Line, Tumor Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Diagnosis Drug therapy Fundamental and applied biological sciences. Psychology Gene Expression Gene Therapy Genetic aspects Health aspects Health. Pharmaceutical industry Human Genetics Immune response Immunotherapy Inbreeding Industrial applications and implications. Economical aspects Innate immunity Mathematical models Mathematics Medical sciences Melanoma Melanoma, Experimental - therapy Mice Mice, Inbred C57BL Models, Theoretical Molecular and cellular biology Nanotechnology Oncolytic Virotherapy - methods original-article Physical training Population dynamics Replication Risk factors Skin cancer Stomatitis Transfusions. Complications. Transfusion reactions. Cell and gene therapy Tumors Vesicular stomatitis Indiana virus - genetics Vesicular stomatitis Indiana virus - immunology Vesicular stomatitis virus Virus Replication Viruses |
| title | Dynamics of melanoma tumor therapy with vesicular stomatitis virus: explaining the variability in outcomes using mathematical modeling |
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