Preclinical evaluation of a class of infectivity-enhanced adenoviral vectors in ovarian cancer gene therapy
Ovarian carcinoma cells are often infected inefficiently by adenoviruses (Ad) due to low expression of coxsackie–adenovirus receptors (CAR), hindering the application of adenovirus-mediated gene therapy in ovarian cancer. In this study, we explored a class of infectivity-enhanced Ad vectors, which c...
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| Veröffentlicht in: | Gene therapy 2004-05, Vol.11 (10), p.874-878 |
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| creator | Wu, H Han, T Lam, J T Leath, C A Dmitriev, I Kashentseva, E Barnes, M N Alvarez, R D Curiel, D T |
| description | Ovarian carcinoma cells are often infected inefficiently by adenoviruses (Ad) due to low expression of coxsackie–adenovirus receptors (CAR), hindering the application of adenovirus-mediated gene therapy in ovarian cancer. In this study, we explored a class of infectivity-enhanced Ad vectors, which contain CAR-independent targeting motifs RGD (Ad5.RGD), polylysine (Ad5.pK7), or both (Ad5.RGD.pK7), for their utility in ovarian cancer gene therapy using
in vitro
and
in vivo
model systems. We found that these vectors infected established ovarian carcinoma cell lines and primary ovarian cancer cells with significantly enhanced infectivity. Among them, Ad5.RGD.pK7 appeared to be most efficient. Further, we evaluated their gene delivery efficiency using two different ovarian cancer mouse models – subcutaneous and intraperitoneal human ovarian cancer xenografts. All of the modified vectors appeared to be more efficient than the unmodified Ad5 vector in both models, although some of the differences are not statistically significant. Of these, Ad5.RGD.pK7 exhibited the highest efficacy in the subcutaneous tumor model, while Ad5.pK7 worked most efficiently in the intraperitoneal tumor model. These preclinical results suggest that Ad5.RGD.pK7 and Ad5.pK7 may be very useful in ovarian cancer gene therapy. |
| doi_str_mv | 10.1038/sj.gt.3302249 |
| format | Article |
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in vitro
and
in vivo
model systems. We found that these vectors infected established ovarian carcinoma cell lines and primary ovarian cancer cells with significantly enhanced infectivity. Among them, Ad5.RGD.pK7 appeared to be most efficient. Further, we evaluated their gene delivery efficiency using two different ovarian cancer mouse models – subcutaneous and intraperitoneal human ovarian cancer xenografts. All of the modified vectors appeared to be more efficient than the unmodified Ad5 vector in both models, although some of the differences are not statistically significant. Of these, Ad5.RGD.pK7 exhibited the highest efficacy in the subcutaneous tumor model, while Ad5.pK7 worked most efficiently in the intraperitoneal tumor model. These preclinical results suggest that Ad5.RGD.pK7 and Ad5.pK7 may be very useful in ovarian cancer gene therapy.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/sj.gt.3302249</identifier><identifier>PMID: 14999229</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adenoviridae - genetics ; Adenoviridae - pathogenicity ; Adenovirus ; Adenoviruses ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animal models ; Animals ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; brief-communication ; Cell Biology ; Coxsackievirus ; Disease Models, Animal ; Expression vectors ; Female ; Female genital diseases ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene Targeting ; Gene Therapy ; Gene transfer ; Gene Transfer Techniques ; Genetic Therapy - methods ; Genetic Vectors ; Gynecology. Andrology. Obstetrics ; Health. Pharmaceutical industry ; Human Genetics ; Humans ; Industrial applications and implications. Economical aspects ; Infectivity ; Medical sciences ; Mice ; Mice, SCID ; Nanotechnology ; Neoplasm Transplantation ; Oligopeptides - genetics ; Ovarian cancer ; Ovarian carcinoma ; Ovarian Neoplasms - therapy ; Polylysine ; Polylysine - genetics ; Statistical analysis ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Tumor cell lines ; Tumor Cells, Cultured ; Tumors ; Vectors (Biology) ; Xenografts</subject><ispartof>Gene therapy, 2004-05, Vol.11 (10), p.874-878</ispartof><rights>Springer Nature Limited 2004</rights><rights>2004 INIST-CNRS</rights><rights>COPYRIGHT 2004 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 2004</rights><rights>Nature Publishing Group 2004.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c614t-9b73368e6ea2bf61ec8690a10a9d7f93678de465ea95e9519254a29e1a9f4e103</citedby><cites>FETCH-LOGICAL-c614t-9b73368e6ea2bf61ec8690a10a9d7f93678de465ea95e9519254a29e1a9f4e103</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.3302249$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.gt.3302249$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15727381$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14999229$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, H</creatorcontrib><creatorcontrib>Han, T</creatorcontrib><creatorcontrib>Lam, J T</creatorcontrib><creatorcontrib>Leath, C A</creatorcontrib><creatorcontrib>Dmitriev, I</creatorcontrib><creatorcontrib>Kashentseva, E</creatorcontrib><creatorcontrib>Barnes, M N</creatorcontrib><creatorcontrib>Alvarez, R D</creatorcontrib><creatorcontrib>Curiel, D T</creatorcontrib><title>Preclinical evaluation of a class of infectivity-enhanced adenoviral vectors in ovarian cancer gene therapy</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><addtitle>Gene Ther</addtitle><description>Ovarian carcinoma cells are often infected inefficiently by adenoviruses (Ad) due to low expression of coxsackie–adenovirus receptors (CAR), hindering the application of adenovirus-mediated gene therapy in ovarian cancer. In this study, we explored a class of infectivity-enhanced Ad vectors, which contain CAR-independent targeting motifs RGD (Ad5.RGD), polylysine (Ad5.pK7), or both (Ad5.RGD.pK7), for their utility in ovarian cancer gene therapy using
in vitro
and
in vivo
model systems. We found that these vectors infected established ovarian carcinoma cell lines and primary ovarian cancer cells with significantly enhanced infectivity. Among them, Ad5.RGD.pK7 appeared to be most efficient. Further, we evaluated their gene delivery efficiency using two different ovarian cancer mouse models – subcutaneous and intraperitoneal human ovarian cancer xenografts. All of the modified vectors appeared to be more efficient than the unmodified Ad5 vector in both models, although some of the differences are not statistically significant. Of these, Ad5.RGD.pK7 exhibited the highest efficacy in the subcutaneous tumor model, while Ad5.pK7 worked most efficiently in the intraperitoneal tumor model. These preclinical results suggest that Ad5.RGD.pK7 and Ad5.pK7 may be very useful in ovarian cancer gene therapy.</description><subject>Adenoviridae - genetics</subject><subject>Adenoviridae - pathogenicity</subject><subject>Adenovirus</subject><subject>Adenoviruses</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animal models</subject><subject>Animals</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>brief-communication</subject><subject>Cell Biology</subject><subject>Coxsackievirus</subject><subject>Disease Models, Animal</subject><subject>Expression vectors</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene Targeting</subject><subject>Gene Therapy</subject><subject>Gene transfer</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Health. Pharmaceutical industry</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Infectivity</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Nanotechnology</subject><subject>Neoplasm Transplantation</subject><subject>Oligopeptides - genetics</subject><subject>Ovarian cancer</subject><subject>Ovarian carcinoma</subject><subject>Ovarian Neoplasms - therapy</subject><subject>Polylysine</subject><subject>Polylysine - genetics</subject><subject>Statistical analysis</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>Tumor cell lines</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>Vectors (Biology)</subject><subject>Xenografts</subject><issn>0969-7128</issn><issn>1476-5462</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqF0s2LEzEUAPBBFLeuHr3KoLjgYWqSySST47L4sbCg-HEOr5k309Rp0k0yxf73prRQK4rkkJD8ksd7eUXxnJI5JXX7Nq7mQ5rXNWGMqwfFjHIpqoYL9rCYESVUJSlrL4onMa4IIVy27HFxQblSijE1K358DmhG66yBscQtjBMk613p-xJKM0KM-6V1PZpktzbtKnRLcAa7Ejp0fmtDvrjNpz7E7Eq_hWDBlWaPQjmgwzItMcBm97R41MMY8dlxviy-v3_37eZjdffpw-3N9V1lBOWpUgtZ16JFgcAWvaBoWqEIUAKqk72qhWw75KJBUA2qhirWcGAKKaieYy7KZXF1eHcT_P2EMem1jQbHERz6KWpJFREyB_kfpFIJIlqZ4as_4MpPweUkNBOci1ooybN6-U9FW0l4o1hG8wMaYESdC-tTAJNHh2trvMPe5v1r2rK2YUTts3lzdiGbhD_TAFOM-vbrl3N79ZtdIoxpGf047b80nsPqAE3wMQbs9SbYNYSdpkTv-0rHlR6SPvZV9i-OqU2LNXYnfWykDF4fAcTcSn3I32_jyTWSybqlp_RjPnIDhlON_h75F-tS4s0</recordid><startdate>20040501</startdate><enddate>20040501</enddate><creator>Wu, H</creator><creator>Han, T</creator><creator>Lam, J T</creator><creator>Leath, C A</creator><creator>Dmitriev, I</creator><creator>Kashentseva, E</creator><creator>Barnes, M N</creator><creator>Alvarez, R D</creator><creator>Curiel, D T</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>7QO</scope><scope>7X8</scope></search><sort><creationdate>20040501</creationdate><title>Preclinical evaluation of a class of infectivity-enhanced adenoviral vectors in ovarian cancer gene therapy</title><author>Wu, H ; Han, T ; Lam, J T ; Leath, C A ; Dmitriev, I ; Kashentseva, E ; Barnes, M N ; Alvarez, R D ; Curiel, D T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c614t-9b73368e6ea2bf61ec8690a10a9d7f93678de465ea95e9519254a29e1a9f4e103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adenoviridae - genetics</topic><topic>Adenoviridae - pathogenicity</topic><topic>Adenovirus</topic><topic>Adenoviruses</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animal models</topic><topic>Animals</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>brief-communication</topic><topic>Cell Biology</topic><topic>Coxsackievirus</topic><topic>Disease Models, Animal</topic><topic>Expression vectors</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene Targeting</topic><topic>Gene Therapy</topic><topic>Gene transfer</topic><topic>Gene Transfer Techniques</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Health. Pharmaceutical industry</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Infectivity</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Nanotechnology</topic><topic>Neoplasm Transplantation</topic><topic>Oligopeptides - genetics</topic><topic>Ovarian cancer</topic><topic>Ovarian carcinoma</topic><topic>Ovarian Neoplasms - therapy</topic><topic>Polylysine</topic><topic>Polylysine - genetics</topic><topic>Statistical analysis</topic><topic>Transfusions. Complications. Transfusion reactions. 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In this study, we explored a class of infectivity-enhanced Ad vectors, which contain CAR-independent targeting motifs RGD (Ad5.RGD), polylysine (Ad5.pK7), or both (Ad5.RGD.pK7), for their utility in ovarian cancer gene therapy using
in vitro
and
in vivo
model systems. We found that these vectors infected established ovarian carcinoma cell lines and primary ovarian cancer cells with significantly enhanced infectivity. Among them, Ad5.RGD.pK7 appeared to be most efficient. Further, we evaluated their gene delivery efficiency using two different ovarian cancer mouse models – subcutaneous and intraperitoneal human ovarian cancer xenografts. All of the modified vectors appeared to be more efficient than the unmodified Ad5 vector in both models, although some of the differences are not statistically significant. Of these, Ad5.RGD.pK7 exhibited the highest efficacy in the subcutaneous tumor model, while Ad5.pK7 worked most efficiently in the intraperitoneal tumor model. These preclinical results suggest that Ad5.RGD.pK7 and Ad5.pK7 may be very useful in ovarian cancer gene therapy.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>14999229</pmid><doi>10.1038/sj.gt.3302249</doi><tpages>5</tpages></addata></record> |
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| ispartof | Gene therapy, 2004-05, Vol.11 (10), p.874-878 |
| issn | 0969-7128 1476-5462 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71906773 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; EZB-FREE-00999 freely available EZB journals |
| subjects | Adenoviridae - genetics Adenoviridae - pathogenicity Adenovirus Adenoviruses Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animal models Animals Applied cell therapy and gene therapy Biological and medical sciences Biomedical and Life Sciences Biomedicine Biotechnology brief-communication Cell Biology Coxsackievirus Disease Models, Animal Expression vectors Female Female genital diseases Fundamental and applied biological sciences. Psychology Gene Expression Gene Targeting Gene Therapy Gene transfer Gene Transfer Techniques Genetic Therapy - methods Genetic Vectors Gynecology. Andrology. Obstetrics Health. Pharmaceutical industry Human Genetics Humans Industrial applications and implications. Economical aspects Infectivity Medical sciences Mice Mice, SCID Nanotechnology Neoplasm Transplantation Oligopeptides - genetics Ovarian cancer Ovarian carcinoma Ovarian Neoplasms - therapy Polylysine Polylysine - genetics Statistical analysis Transfusions. Complications. Transfusion reactions. Cell and gene therapy Tumor cell lines Tumor Cells, Cultured Tumors Vectors (Biology) Xenografts |
| title | Preclinical evaluation of a class of infectivity-enhanced adenoviral vectors in ovarian cancer gene therapy |
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