Destruction of Nonimmunogenic Mammary Tumor Cells by a Fusogenic Oncolytic Herpes Simplex Virus Induces Potent Antitumor Immunity
In principle, destruction of tumor cells in vivo by oncolytic agents would release the entire repertoire of tumor antigens in their natural forms, leading to effective antitumor immunity. This goal has been elusive despite extensive testing of numerous strategies. We developed a doubly fusogenic onc...
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Veröffentlicht in: | Molecular therapy 2004-05, Vol.9 (5), p.658-665 |
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creator | Nakamori, Mikihito Fu, Xinping Rousseau, Raphael Chen, Si-Yi Zhang, Xiaoliu |
description | In principle, destruction of tumor cells in vivo by oncolytic agents would release the entire repertoire of tumor antigens in their natural forms, leading to effective antitumor immunity. This goal has been elusive despite extensive testing of numerous strategies. We developed a doubly fusogenic oncolytic herpes simplex virus (Synco-2D) that kills tumor cells by a unique dual mechanism combining direct cytolysis with syncytial formation induced by cell membrane fusion. A single intratumor injection of Synco-2D induced strong antitumor immunity against an otherwise nonimmunogenic murine mammary tumor growing in immune-competent mice. CD8+ T cells were the primary mediators of immunity, contributing to the destruction of both primary and metastatic tumors. We conclude that the fusogenic capacity of Synco-2D enables it to elicit antitumor immunity exceeding that induced by more conventional oncolytic viruses. |
doi_str_mv | 10.1016/j.ymthe.2004.02.019 |
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This goal has been elusive despite extensive testing of numerous strategies. We developed a doubly fusogenic oncolytic herpes simplex virus (Synco-2D) that kills tumor cells by a unique dual mechanism combining direct cytolysis with syncytial formation induced by cell membrane fusion. A single intratumor injection of Synco-2D induced strong antitumor immunity against an otherwise nonimmunogenic murine mammary tumor growing in immune-competent mice. CD8+ T cells were the primary mediators of immunity, contributing to the destruction of both primary and metastatic tumors. 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We conclude that the fusogenic capacity of Synco-2D enables it to elicit antitumor immunity exceeding that induced by more conventional oncolytic viruses.</description><subject>Animals</subject><subject>Antigens</subject><subject>Carcinoma - immunology</subject><subject>Carcinoma - virology</subject><subject>Cell Line</subject><subject>Cell Survival</subject><subject>Cytotoxicity</subject><subject>Drug dosages</subject><subject>Female</subject><subject>Gene therapy</subject><subject>Herpes viruses</subject><subject>Immunotherapy</subject><subject>Infections</subject><subject>Interferon-gamma - immunology</subject><subject>Interleukin-10 - immunology</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - secondary</subject><subject>Lymphocyte Depletion</subject><subject>Mammary Neoplasms, Experimental - immunology</subject><subject>Mammary Neoplasms, Experimental - virology</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Membrane Fusion</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Neoplasm Metastasis - pathology</subject><subject>Neoplasm Transplantation</subject><subject>Simplexvirus - physiology</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Tumor Escape - immunology</subject><subject>Tumors</subject><subject>Vaccines</subject><issn>1525-0016</issn><issn>1525-0024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkV1rFDEUhoNYbK3-AkECgnc75mSS-bgsW2sXalvo4m3IZjKaZZKs-QDn0n9upl1a8Covh-e855y8CH0AUgGB5su-mm36pStKCKsIrQj0r9AZcMpXhFD2-llDc4rexrgvCnjfvEGnwIGSmjZn6O-ljilklYx32I_41jtjbXb-p3ZG4e_SWhlmvM3WB7zW0xTxbsYSX-V4RO6c8tOcirrW4aAjfjD2MOk_-IcJOeKNG7Iq1XuftEv4wiWTHs02yxiT5nfoZJRT1O-P7znaXn3drq9XN3ffNuuLm5ViTZ1WTd3tODDFOVFDTzvaNqztJa-V6tlQM8J60IxLOeoW6ACkbQboxh0rBd6p-hx9frI9BP87l6OFNVGVg6TTPkfRQtcDJ7SAn_4D9z4HV1YT0JbBNeOkK1T9RKngYwx6FIdglq8SQMQSj9iLx3jEEo8gVJR4StfHo3feWT289BzzeAGcTDnoZ8Cmxabr6n9GaZij</recordid><startdate>20040501</startdate><enddate>20040501</enddate><creator>Nakamori, Mikihito</creator><creator>Fu, Xinping</creator><creator>Rousseau, Raphael</creator><creator>Chen, Si-Yi</creator><creator>Zhang, Xiaoliu</creator><general>Elsevier Limited</general><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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20040501</creationdate><title>Destruction of Nonimmunogenic Mammary Tumor Cells by a Fusogenic Oncolytic Herpes Simplex Virus Induces Potent Antitumor Immunity</title><author>Nakamori, Mikihito ; Fu, Xinping ; Rousseau, Raphael ; Chen, Si-Yi ; Zhang, Xiaoliu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-638b514c550cd928276479a53cc94d340491e45aafe712d1076d18fb4afe58c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Antigens</topic><topic>Carcinoma - immunology</topic><topic>Carcinoma - virology</topic><topic>Cell Line</topic><topic>Cell Survival</topic><topic>Cytotoxicity</topic><topic>Drug dosages</topic><topic>Female</topic><topic>Gene therapy</topic><topic>Herpes viruses</topic><topic>Immunotherapy</topic><topic>Infections</topic><topic>Interferon-gamma - immunology</topic><topic>Interleukin-10 - immunology</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - secondary</topic><topic>Lymphocyte Depletion</topic><topic>Mammary Neoplasms, Experimental - immunology</topic><topic>Mammary Neoplasms, Experimental - virology</topic><topic>Medical schools</topic><topic>Medicine</topic><topic>Membrane Fusion</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Neoplasm Metastasis - pathology</topic><topic>Neoplasm Transplantation</topic><topic>Simplexvirus - physiology</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Tumor Escape - immunology</topic><topic>Tumors</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nakamori, Mikihito</creatorcontrib><creatorcontrib>Fu, Xinping</creatorcontrib><creatorcontrib>Rousseau, Raphael</creatorcontrib><creatorcontrib>Chen, Si-Yi</creatorcontrib><creatorcontrib>Zhang, Xiaoliu</creatorcontrib><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>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>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</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>Biological Science Database</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>MEDLINE - Academic</collection><jtitle>Molecular therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nakamori, Mikihito</au><au>Fu, Xinping</au><au>Rousseau, Raphael</au><au>Chen, Si-Yi</au><au>Zhang, Xiaoliu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Destruction of Nonimmunogenic Mammary Tumor Cells by a Fusogenic Oncolytic Herpes Simplex Virus Induces Potent Antitumor Immunity</atitle><jtitle>Molecular therapy</jtitle><addtitle>Mol Ther</addtitle><date>2004-05-01</date><risdate>2004</risdate><volume>9</volume><issue>5</issue><spage>658</spage><epage>665</epage><pages>658-665</pages><issn>1525-0016</issn><eissn>1525-0024</eissn><abstract>In principle, destruction of tumor cells in vivo by oncolytic agents would release the entire repertoire of tumor antigens in their natural forms, leading to effective antitumor immunity. 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subjects | Animals Antigens Carcinoma - immunology Carcinoma - virology Cell Line Cell Survival Cytotoxicity Drug dosages Female Gene therapy Herpes viruses Immunotherapy Infections Interferon-gamma - immunology Interleukin-10 - immunology Lung Neoplasms - pathology Lung Neoplasms - secondary Lymphocyte Depletion Mammary Neoplasms, Experimental - immunology Mammary Neoplasms, Experimental - virology Medical schools Medicine Membrane Fusion Metastasis Mice Mice, Inbred BALB C Neoplasm Metastasis - pathology Neoplasm Transplantation Simplexvirus - physiology T-Lymphocytes, Cytotoxic - immunology Tumor Escape - immunology Tumors Vaccines |
title | Destruction of Nonimmunogenic Mammary Tumor Cells by a Fusogenic Oncolytic Herpes Simplex Virus Induces Potent Antitumor Immunity |
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