Biological purging of breast cancer cell lines using a replication-competent oncolytic virus in human stem cell autografts
Autologous hematological stem cell transplantation (ASCT) is used for the treatment of many hematological and several solid cancers. ASCT, however, has proven disappointing as a therapeutic strategy for breast cancer. Our group and others have previously shown that breast cancer micrometastases foun...
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| Veröffentlicht in: | Bone marrow transplantation (Basingstoke) 2005-06, Vol.35 (11), p.1055-1064 |
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| container_title | Bone marrow transplantation (Basingstoke) |
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| creator | THIRUKKUMARAN, C. M LUIDER, J. M STEWART, D. A ALAIN, T RUSSELL, J. A AUER, I. A FORSYTH, P MORRIS, D. G |
| description | Autologous hematological stem cell transplantation (ASCT) is used for the treatment of many hematological and several solid cancers. ASCT, however, has proven disappointing as a therapeutic strategy for breast cancer. Our group and others have previously shown that breast cancer micrometastases found in patients' apheresis products (APs) predict shorter progression-free and overall survival. The implications of this finding are twofold: (i) contaminating tumor cells (CTCs) in AP reflect a higher systemic disease burden and/or (ii) reinfused CTCs contribute to relapse/progressive disease. To date, purging strategies have been disappointing. We have previously demonstrated the oncolytic properties of reovirus in in vitro, in vivo and ex vivo systems. In the present study, we tested the hypothesis that reovirus purges CTCs in a breast cancer cell line purging model. Reovirus-infected human breast cancer cell lines (HTB 133, HTB 132, SKBR3 and MCF7) exhibited cell death within days. Admixtures of AP with cells from breast tumor cell lines, which were then exposed to reovirus, showed complete purging of CTCs (assessed via flow cytometry/tumor cell outgrowth analysis) without deleterious effect on CD34+ cells. Our results provide preclinical support for the ex vivo use of reovirus as a purging modality for breast cancer during ASCT. |
| doi_str_mv | 10.1038/sj.bmt.1704931 |
| format | Article |
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M ; LUIDER, J. M ; STEWART, D. A ; ALAIN, T ; RUSSELL, J. A ; AUER, I. A ; FORSYTH, P ; MORRIS, D. G</creator><creatorcontrib>THIRUKKUMARAN, C. M ; LUIDER, J. M ; STEWART, D. A ; ALAIN, T ; RUSSELL, J. A ; AUER, I. A ; FORSYTH, P ; MORRIS, D. G</creatorcontrib><description>Autologous hematological stem cell transplantation (ASCT) is used for the treatment of many hematological and several solid cancers. ASCT, however, has proven disappointing as a therapeutic strategy for breast cancer. Our group and others have previously shown that breast cancer micrometastases found in patients' apheresis products (APs) predict shorter progression-free and overall survival. The implications of this finding are twofold: (i) contaminating tumor cells (CTCs) in AP reflect a higher systemic disease burden and/or (ii) reinfused CTCs contribute to relapse/progressive disease. To date, purging strategies have been disappointing. We have previously demonstrated the oncolytic properties of reovirus in in vitro, in vivo and ex vivo systems. In the present study, we tested the hypothesis that reovirus purges CTCs in a breast cancer cell line purging model. Reovirus-infected human breast cancer cell lines (HTB 133, HTB 132, SKBR3 and MCF7) exhibited cell death within days. Admixtures of AP with cells from breast tumor cell lines, which were then exposed to reovirus, showed complete purging of CTCs (assessed via flow cytometry/tumor cell outgrowth analysis) without deleterious effect on CD34+ cells. Our results provide preclinical support for the ex vivo use of reovirus as a purging modality for breast cancer during ASCT.</description><identifier>ISSN: 0268-3369</identifier><identifier>EISSN: 1476-5365</identifier><identifier>DOI: 10.1038/sj.bmt.1704931</identifier><identifier>PMID: 15821774</identifier><identifier>CODEN: BMTRE9</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>Admixtures ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Antigens, CD34 - biosynthesis ; Apheresis ; Autografts ; Biological and medical sciences ; Blood Component Removal ; Bone marrow ; Bone Marrow Purging - methods ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Breast cancer ; Breast Neoplasms - therapy ; Care and treatment ; CD34 antigen ; Cell death ; Cell Line, Tumor ; Complications and side effects ; Disease Progression ; Disease-Free Survival ; DNA Fragmentation ; Flow Cytometry ; Hematology ; Hematopoietic stem cells ; Hematopoietic Stem Cells - cytology ; Humans ; Immunohistochemistry ; Immunoprecipitation ; In vivo methods and tests ; Leukocyte Common Antigens - biosynthesis ; Medical sciences ; Methionine - chemistry ; Methods ; Oncolysis ; Physiological aspects ; Prognosis ; Purging ; Reoviruses ; Stem cell transplantation ; Stem Cell Transplantation - methods ; Stem cells ; Time Factors ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Transplantation ; Transplantation, Autologous ; Treatment Outcome ; Tumor cell lines ; Tumor cells ; Tumors ; Viruses ; Viruses - genetics</subject><ispartof>Bone marrow transplantation (Basingstoke), 2005-06, Vol.35 (11), p.1055-1064</ispartof><rights>2005 INIST-CNRS</rights><rights>COPYRIGHT 2005 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2005</rights><rights>Nature Publishing Group 2005.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c516t-ebf0b2b819f36acac69f8a4679180c6cfe9531e5bd43b8a7adbf886ebc40f6c83</citedby><cites>FETCH-LOGICAL-c516t-ebf0b2b819f36acac69f8a4679180c6cfe9531e5bd43b8a7adbf886ebc40f6c83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16801232$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15821774$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>THIRUKKUMARAN, C. M</creatorcontrib><creatorcontrib>LUIDER, J. M</creatorcontrib><creatorcontrib>STEWART, D. A</creatorcontrib><creatorcontrib>ALAIN, T</creatorcontrib><creatorcontrib>RUSSELL, J. A</creatorcontrib><creatorcontrib>AUER, I. A</creatorcontrib><creatorcontrib>FORSYTH, P</creatorcontrib><creatorcontrib>MORRIS, D. G</creatorcontrib><title>Biological purging of breast cancer cell lines using a replication-competent oncolytic virus in human stem cell autografts</title><title>Bone marrow transplantation (Basingstoke)</title><addtitle>Bone Marrow Transplant</addtitle><description>Autologous hematological stem cell transplantation (ASCT) is used for the treatment of many hematological and several solid cancers. ASCT, however, has proven disappointing as a therapeutic strategy for breast cancer. Our group and others have previously shown that breast cancer micrometastases found in patients' apheresis products (APs) predict shorter progression-free and overall survival. The implications of this finding are twofold: (i) contaminating tumor cells (CTCs) in AP reflect a higher systemic disease burden and/or (ii) reinfused CTCs contribute to relapse/progressive disease. To date, purging strategies have been disappointing. We have previously demonstrated the oncolytic properties of reovirus in in vitro, in vivo and ex vivo systems. In the present study, we tested the hypothesis that reovirus purges CTCs in a breast cancer cell line purging model. Reovirus-infected human breast cancer cell lines (HTB 133, HTB 132, SKBR3 and MCF7) exhibited cell death within days. Admixtures of AP with cells from breast tumor cell lines, which were then exposed to reovirus, showed complete purging of CTCs (assessed via flow cytometry/tumor cell outgrowth analysis) without deleterious effect on CD34+ cells. Our results provide preclinical support for the ex vivo use of reovirus as a purging modality for breast cancer during ASCT.</description><subject>Admixtures</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Antigens, CD34 - biosynthesis</subject><subject>Apheresis</subject><subject>Autografts</subject><subject>Biological and medical sciences</subject><subject>Blood Component Removal</subject><subject>Bone marrow</subject><subject>Bone Marrow Purging - methods</subject><subject>Bone marrow, stem cells transplantation. Graft versus host reaction</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - therapy</subject><subject>Care and treatment</subject><subject>CD34 antigen</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Complications and side effects</subject><subject>Disease Progression</subject><subject>Disease-Free Survival</subject><subject>DNA Fragmentation</subject><subject>Flow Cytometry</subject><subject>Hematology</subject><subject>Hematopoietic stem cells</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunoprecipitation</subject><subject>In vivo methods and tests</subject><subject>Leukocyte Common Antigens - biosynthesis</subject><subject>Medical sciences</subject><subject>Methionine - chemistry</subject><subject>Methods</subject><subject>Oncolysis</subject><subject>Physiological aspects</subject><subject>Prognosis</subject><subject>Purging</subject><subject>Reoviruses</subject><subject>Stem cell transplantation</subject><subject>Stem Cell Transplantation - methods</subject><subject>Stem cells</subject><subject>Time Factors</subject><subject>Transfusions. Complications. Transfusion reactions. 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Complications. Transfusion reactions. Cell and gene therapy</topic><topic>Transplantation</topic><topic>Transplantation, Autologous</topic><topic>Treatment Outcome</topic><topic>Tumor cell lines</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Viruses</topic><topic>Viruses - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>THIRUKKUMARAN, C. M</creatorcontrib><creatorcontrib>LUIDER, J. M</creatorcontrib><creatorcontrib>STEWART, D. A</creatorcontrib><creatorcontrib>ALAIN, T</creatorcontrib><creatorcontrib>RUSSELL, J. A</creatorcontrib><creatorcontrib>AUER, I. A</creatorcontrib><creatorcontrib>FORSYTH, P</creatorcontrib><creatorcontrib>MORRIS, D. 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M</au><au>LUIDER, J. M</au><au>STEWART, D. A</au><au>ALAIN, T</au><au>RUSSELL, J. A</au><au>AUER, I. A</au><au>FORSYTH, P</au><au>MORRIS, D. G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biological purging of breast cancer cell lines using a replication-competent oncolytic virus in human stem cell autografts</atitle><jtitle>Bone marrow transplantation (Basingstoke)</jtitle><addtitle>Bone Marrow Transplant</addtitle><date>2005-06-01</date><risdate>2005</risdate><volume>35</volume><issue>11</issue><spage>1055</spage><epage>1064</epage><pages>1055-1064</pages><issn>0268-3369</issn><eissn>1476-5365</eissn><coden>BMTRE9</coden><abstract>Autologous hematological stem cell transplantation (ASCT) is used for the treatment of many hematological and several solid cancers. ASCT, however, has proven disappointing as a therapeutic strategy for breast cancer. Our group and others have previously shown that breast cancer micrometastases found in patients' apheresis products (APs) predict shorter progression-free and overall survival. The implications of this finding are twofold: (i) contaminating tumor cells (CTCs) in AP reflect a higher systemic disease burden and/or (ii) reinfused CTCs contribute to relapse/progressive disease. To date, purging strategies have been disappointing. We have previously demonstrated the oncolytic properties of reovirus in in vitro, in vivo and ex vivo systems. In the present study, we tested the hypothesis that reovirus purges CTCs in a breast cancer cell line purging model. Reovirus-infected human breast cancer cell lines (HTB 133, HTB 132, SKBR3 and MCF7) exhibited cell death within days. Admixtures of AP with cells from breast tumor cell lines, which were then exposed to reovirus, showed complete purging of CTCs (assessed via flow cytometry/tumor cell outgrowth analysis) without deleterious effect on CD34+ cells. Our results provide preclinical support for the ex vivo use of reovirus as a purging modality for breast cancer during ASCT.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>15821774</pmid><doi>10.1038/sj.bmt.1704931</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0268-3369 |
| ispartof | Bone marrow transplantation (Basingstoke), 2005-06, Vol.35 (11), p.1055-1064 |
| issn | 0268-3369 1476-5365 |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online; EZB-FREE-00999 freely available EZB journals |
| subjects | Admixtures Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Antigens, CD34 - biosynthesis Apheresis Autografts Biological and medical sciences Blood Component Removal Bone marrow Bone Marrow Purging - methods Bone marrow, stem cells transplantation. Graft versus host reaction Breast cancer Breast Neoplasms - therapy Care and treatment CD34 antigen Cell death Cell Line, Tumor Complications and side effects Disease Progression Disease-Free Survival DNA Fragmentation Flow Cytometry Hematology Hematopoietic stem cells Hematopoietic Stem Cells - cytology Humans Immunohistochemistry Immunoprecipitation In vivo methods and tests Leukocyte Common Antigens - biosynthesis Medical sciences Methionine - chemistry Methods Oncolysis Physiological aspects Prognosis Purging Reoviruses Stem cell transplantation Stem Cell Transplantation - methods Stem cells Time Factors Transfusions. Complications. Transfusion reactions. Cell and gene therapy Transplantation Transplantation, Autologous Treatment Outcome Tumor cell lines Tumor cells Tumors Viruses Viruses - genetics |
| title | Biological purging of breast cancer cell lines using a replication-competent oncolytic virus in human stem cell autografts |
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