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Adenovirus-Mediated Interleukin-12 Gene Therapy for Metastatic Colon Carcinoma
Recombinant adenoviral mediated delivery of suicide and cytokine genes has been investigated as a treatment for hepatic metastases of colon carcinoma in mice. Liver tumors were established by intrahepatic implantation of a poorly immunogenic colon carcinoma cell line (MCA-26), which is syngeneic in...
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| Published in: | Proceedings of the National Academy of Sciences - PNAS 1996-10, Vol.93 (21), p.11302-11306 |
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| Main Authors: | , , , , , , , |
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| Language: | English |
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| container_end_page | 11306 |
| container_issue | 21 |
| container_start_page | 11302 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 93 |
| creator | Caruso, Manuel Pham-Nguyen, Khiem Kwong, Yok-Lam Xu, Bisong Kosai, Ken-Ichiro Finegold, Milton Savio L. C. Woo Chen, Shu-Hsia |
| description | Recombinant adenoviral mediated delivery of suicide and cytokine genes has been investigated as a treatment for hepatic metastases of colon carcinoma in mice. Liver tumors were established by intrahepatic implantation of a poorly immunogenic colon carcinoma cell line (MCA-26), which is syngeneic in BALB/c mice. Intratumoral transfer of the herpes simplex virus type 1 thymidine kinase (HSV-tk) and the murine interleukin (mIL)-2 genes resulted in substantial hepatic tumor regression, induced an effective systemic antitumoral immunity in the host and prolonged the median survival time of the treated animals from 22 to 35 days. The antitumoral immunity declined gradually, which led to tumor recurrence over time. A recombinant adenovirus expressing the mIL-12 gene was constructed and tested in the MCA-26 tumor model. Intratumoral administration of this cytokine vector alone increased significantly survival time of the animals with 25% of the treated animals still living over 70 days. These data indicate that local expression of IL-12 may also be an attractive treatment strategy for metastatic colon carcinoma. |
| doi_str_mv | 10.1073/pnas.93.21.11302 |
| format | article |
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C. Woo ; Chen, Shu-Hsia</creator><creatorcontrib>Caruso, Manuel ; Pham-Nguyen, Khiem ; Kwong, Yok-Lam ; Xu, Bisong ; Kosai, Ken-Ichiro ; Finegold, Milton ; Savio L. C. Woo ; Chen, Shu-Hsia</creatorcontrib><description>Recombinant adenoviral mediated delivery of suicide and cytokine genes has been investigated as a treatment for hepatic metastases of colon carcinoma in mice. Liver tumors were established by intrahepatic implantation of a poorly immunogenic colon carcinoma cell line (MCA-26), which is syngeneic in BALB/c mice. Intratumoral transfer of the herpes simplex virus type 1 thymidine kinase (HSV-tk) and the murine interleukin (mIL)-2 genes resulted in substantial hepatic tumor regression, induced an effective systemic antitumoral immunity in the host and prolonged the median survival time of the treated animals from 22 to 35 days. The antitumoral immunity declined gradually, which led to tumor recurrence over time. A recombinant adenovirus expressing the mIL-12 gene was constructed and tested in the MCA-26 tumor model. Intratumoral administration of this cytokine vector alone increased significantly survival time of the animals with 25% of the treated animals still living over 70 days. These data indicate that local expression of IL-12 may also be an attractive treatment strategy for metastatic colon carcinoma.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.93.21.11302</identifier><identifier>PMID: 8876130</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Adenoviridae ; adenovirus ; Animals ; Cancer ; Carcinoma ; Cell Line ; Cell lines ; Cellular biology ; Colon cancer ; Colonic Neoplasms - immunology ; Colonic Neoplasms - pathology ; Colonic Neoplasms - therapy ; Cytokines ; Gene therapy ; Genetic Therapy ; Genetic Vectors ; herpes simplex virus 1 ; Interleukin-12 - genetics ; Interleukin-12 - therapeutic use ; Liver ; Liver Neoplasms - immunology ; Liver Neoplasms - pathology ; Liver Neoplasms - secondary ; Liver Neoplasms - therapy ; Mice ; Mice, Inbred BALB C ; Natural killer cells ; Papers from a Colloquium ; Recombinant Proteins - biosynthesis ; T lymphocytes ; T-Lymphocytes, Cytotoxic - immunology ; Thymidine Kinase - biosynthesis ; Tumors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1996-10, Vol.93 (21), p.11302-11306</ispartof><rights>Copyright 1996 National Academy of Sciences</rights><rights>Copyright National Academy of Sciences Oct 15, 1996</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c589t-52ce3d592eb0479ca1d97981254657b3a0b6b9413a4cf42987ab3e44f4a1ec8d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/93/21.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/40429$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/40429$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793,58238,58471</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8876130$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Caruso, Manuel</creatorcontrib><creatorcontrib>Pham-Nguyen, Khiem</creatorcontrib><creatorcontrib>Kwong, Yok-Lam</creatorcontrib><creatorcontrib>Xu, Bisong</creatorcontrib><creatorcontrib>Kosai, Ken-Ichiro</creatorcontrib><creatorcontrib>Finegold, Milton</creatorcontrib><creatorcontrib>Savio L. C. Woo</creatorcontrib><creatorcontrib>Chen, Shu-Hsia</creatorcontrib><title>Adenovirus-Mediated Interleukin-12 Gene Therapy for Metastatic Colon Carcinoma</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Recombinant adenoviral mediated delivery of suicide and cytokine genes has been investigated as a treatment for hepatic metastases of colon carcinoma in mice. Liver tumors were established by intrahepatic implantation of a poorly immunogenic colon carcinoma cell line (MCA-26), which is syngeneic in BALB/c mice. Intratumoral transfer of the herpes simplex virus type 1 thymidine kinase (HSV-tk) and the murine interleukin (mIL)-2 genes resulted in substantial hepatic tumor regression, induced an effective systemic antitumoral immunity in the host and prolonged the median survival time of the treated animals from 22 to 35 days. The antitumoral immunity declined gradually, which led to tumor recurrence over time. A recombinant adenovirus expressing the mIL-12 gene was constructed and tested in the MCA-26 tumor model. Intratumoral administration of this cytokine vector alone increased significantly survival time of the animals with 25% of the treated animals still living over 70 days. These data indicate that local expression of IL-12 may also be an attractive treatment strategy for metastatic colon carcinoma.</description><subject>Adenoviridae</subject><subject>adenovirus</subject><subject>Animals</subject><subject>Cancer</subject><subject>Carcinoma</subject><subject>Cell Line</subject><subject>Cell lines</subject><subject>Cellular biology</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms - immunology</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colonic Neoplasms - therapy</subject><subject>Cytokines</subject><subject>Gene therapy</subject><subject>Genetic Therapy</subject><subject>Genetic Vectors</subject><subject>herpes simplex virus 1</subject><subject>Interleukin-12 - genetics</subject><subject>Interleukin-12 - therapeutic use</subject><subject>Liver</subject><subject>Liver Neoplasms - immunology</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - secondary</subject><subject>Liver Neoplasms - therapy</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Natural killer cells</subject><subject>Papers from a Colloquium</subject><subject>Recombinant Proteins - biosynthesis</subject><subject>T lymphocytes</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Thymidine Kinase - biosynthesis</subject><subject>Tumors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><recordid>eNqFkc1v1DAQxS0EKqVwR0iIiAPikmX8kdiWuFQrKJVauJSz5TgTmiVrb22nov89XnZZFQ5w8uH93hvPPEKeU1hQkPzdxtu00HzB6IJSDuwBOaagad0KDQ_JMQCTtRJMPCZPUloBgG4UHJEjpWRb-GPy-bRHH27HOKf6EvvRZuyrc58xTjh_H31NWXWGHqura4x2c1cNIVaXmG3KNo-uWoYp-Gppoxt9WNun5NFgp4TP9u8J-frxw9XyU33x5ex8eXpRu0bpXDfMIe8bzbADIbWztNdSK8oa0Tay4xa6ttOCcivcIJhW0nYchRiEpehUz0_I-13uZu7W2Dv0OdrJbOK4tvHOBDuaPxU_Xptv4dZwBQ0r9jd7eww3M6Zs1mNyOE3WY5iTkUo0vFXyvyBtpOAAqoCv_wJXYY6-3MAwoLwtQ7dpsINcDClFHA4fpmC2fZptn0Zzw6j51WexvLy_6MGwL7Dob_f61vlbvZdghnmaMv7IBX31b7QQL3bEKuUQD4iAUgH_CUPrvQY</recordid><startdate>19961015</startdate><enddate>19961015</enddate><creator>Caruso, Manuel</creator><creator>Pham-Nguyen, Khiem</creator><creator>Kwong, Yok-Lam</creator><creator>Xu, Bisong</creator><creator>Kosai, Ken-Ichiro</creator><creator>Finegold, Milton</creator><creator>Savio L. 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Woo</creator><creator>Chen, Shu-Hsia</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7QO</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19961015</creationdate><title>Adenovirus-Mediated Interleukin-12 Gene Therapy for Metastatic Colon Carcinoma</title><author>Caruso, Manuel ; Pham-Nguyen, Khiem ; Kwong, Yok-Lam ; Xu, Bisong ; Kosai, Ken-Ichiro ; Finegold, Milton ; Savio L. 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Intratumoral transfer of the herpes simplex virus type 1 thymidine kinase (HSV-tk) and the murine interleukin (mIL)-2 genes resulted in substantial hepatic tumor regression, induced an effective systemic antitumoral immunity in the host and prolonged the median survival time of the treated animals from 22 to 35 days. The antitumoral immunity declined gradually, which led to tumor recurrence over time. A recombinant adenovirus expressing the mIL-12 gene was constructed and tested in the MCA-26 tumor model. Intratumoral administration of this cytokine vector alone increased significantly survival time of the animals with 25% of the treated animals still living over 70 days. These data indicate that local expression of IL-12 may also be an attractive treatment strategy for metastatic colon carcinoma.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>8876130</pmid><doi>10.1073/pnas.93.21.11302</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1996-10, Vol.93 (21), p.11302-11306 |
| issn | 0027-8424 1091-6490 |
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| source | Open Access: PubMed Central; JSTOR Archival Journals and Primary Sources Collection |
| subjects | Adenoviridae adenovirus Animals Cancer Carcinoma Cell Line Cell lines Cellular biology Colon cancer Colonic Neoplasms - immunology Colonic Neoplasms - pathology Colonic Neoplasms - therapy Cytokines Gene therapy Genetic Therapy Genetic Vectors herpes simplex virus 1 Interleukin-12 - genetics Interleukin-12 - therapeutic use Liver Liver Neoplasms - immunology Liver Neoplasms - pathology Liver Neoplasms - secondary Liver Neoplasms - therapy Mice Mice, Inbred BALB C Natural killer cells Papers from a Colloquium Recombinant Proteins - biosynthesis T lymphocytes T-Lymphocytes, Cytotoxic - immunology Thymidine Kinase - biosynthesis Tumors |
| title | Adenovirus-Mediated Interleukin-12 Gene Therapy for Metastatic Colon Carcinoma |
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