IL-15 Enhances the in vivo Antitumor Activity of Tumor-Reactive CD8+T Cells
IL-15 and IL-2 possess similar properties, including the ability to induce T cell proliferation. However, whereas IL-2 can promote apoptosis and limit CD8+memory T cell survival and proliferation, IL-15 helps maintain a memory CD8+T cell population and can inhibit apoptosis. We sought to determine w...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2004-02, Vol.101 (7), p.1969-1974 |
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| container_end_page | 1974 |
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| container_issue | 7 |
| container_start_page | 1969 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 101 |
| creator | Klebanoff, Christopher A. Finkelstein, Steven E. Surman, Deborah R. Lichtman, Michael K. Gattinoni, Luca Theoret, Marc R. Grewal, Navrose Spiess, Paul J. Antony, Paul A. Palmer, Douglas C. Tagaya, Yutaka Rosenberg, Steven A. Waldmann, Thomas A. Restifo, Nicholas P. |
| description | IL-15 and IL-2 possess similar properties, including the ability to induce T cell proliferation. However, whereas IL-2 can promote apoptosis and limit CD8+memory T cell survival and proliferation, IL-15 helps maintain a memory CD8+T cell population and can inhibit apoptosis. We sought to determine whether IL-15 could enhance the in vivo function of tumor/self-reactive CD8+T cells by using a T cell receptor transgenic mouse (pmel-1) whose CD8+T cells recognize an epitope derived from the self/melanoma antigen gp100. By removing endogenous IL-15 by using tumor-bearing IL-15 knockout hosts or supplementing IL-15 by means of exogenous administration, as a component of culture media or as a transgene expressed by adoptively transferred T cells, we demonstrate that IL-15 can improve the in vivo antitumor activity of adoptively transferred CD8+T cells. These results provide several avenues for improving adoptive immunotherapy of cancer in patients. |
| doi_str_mv | 10.1073/pnas.0307298101 |
| format | Article |
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However, whereas IL-2 can promote apoptosis and limit CD8+memory T cell survival and proliferation, IL-15 helps maintain a memory CD8+T cell population and can inhibit apoptosis. We sought to determine whether IL-15 could enhance the in vivo function of tumor/self-reactive CD8+T cells by using a T cell receptor transgenic mouse (pmel-1) whose CD8+T cells recognize an epitope derived from the self/melanoma antigen gp100. By removing endogenous IL-15 by using tumor-bearing IL-15 knockout hosts or supplementing IL-15 by means of exogenous administration, as a component of culture media or as a transgene expressed by adoptively transferred T cells, we demonstrate that IL-15 can improve the in vivo antitumor activity of adoptively transferred CD8+T cells. These results provide several avenues for improving adoptive immunotherapy of cancer in patients.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0307298101</identifier><identifier>PMID: 14762166</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adoptive Transfer ; Animals ; Biological Sciences ; Cancer ; CD8-Positive T-Lymphocytes - cytology ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; CD8-Positive T-Lymphocytes - transplantation ; Cells, Cultured ; Culture media ; Cultured cells ; Cytokines ; Female ; Genes ; gp100 Melanoma Antigen ; Humans ; Immunology ; Immunotherapy ; Interleukin-15 - genetics ; Interleukin-15 - immunology ; Interleukin-15 - pharmacology ; Interleukin-2 - immunology ; Interleukin-2 - pharmacology ; Melanoma, Experimental - immunology ; Membrane Glycoproteins - immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Neoplasm Proteins - immunology ; Receptors ; Receptors, Antigen, T-Cell - genetics ; Receptors, Antigen, T-Cell - immunology ; Rodents ; Splenocytes ; T cell receptors ; T lymphocytes ; Tumors ; Vaccination</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2004-02, Vol.101 (7), p.1969-1974</ispartof><rights>Copyright 1993/2004 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Feb 17, 2004</rights><rights>Copyright © 2004, The National Academy of Sciences 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-92deede19a0eafe9f74dd71886392bd710410c5b53dc5a949a3c2485aecda2293</citedby><cites>FETCH-LOGICAL-c539t-92deede19a0eafe9f74dd71886392bd710410c5b53dc5a949a3c2485aecda2293</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/101/7.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3371379$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3371379$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,729,782,786,805,887,27931,27932,53798,53800,58024,58257</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14762166$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Klebanoff, Christopher A.</creatorcontrib><creatorcontrib>Finkelstein, Steven E.</creatorcontrib><creatorcontrib>Surman, Deborah R.</creatorcontrib><creatorcontrib>Lichtman, Michael K.</creatorcontrib><creatorcontrib>Gattinoni, Luca</creatorcontrib><creatorcontrib>Theoret, Marc R.</creatorcontrib><creatorcontrib>Grewal, Navrose</creatorcontrib><creatorcontrib>Spiess, Paul J.</creatorcontrib><creatorcontrib>Antony, Paul A.</creatorcontrib><creatorcontrib>Palmer, Douglas C.</creatorcontrib><creatorcontrib>Tagaya, Yutaka</creatorcontrib><creatorcontrib>Rosenberg, Steven A.</creatorcontrib><creatorcontrib>Waldmann, Thomas A.</creatorcontrib><creatorcontrib>Restifo, Nicholas P.</creatorcontrib><title>IL-15 Enhances the in vivo Antitumor Activity of Tumor-Reactive CD8+T Cells</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>IL-15 and IL-2 possess similar properties, including the ability to induce T cell proliferation. However, whereas IL-2 can promote apoptosis and limit CD8+memory T cell survival and proliferation, IL-15 helps maintain a memory CD8+T cell population and can inhibit apoptosis. We sought to determine whether IL-15 could enhance the in vivo function of tumor/self-reactive CD8+T cells by using a T cell receptor transgenic mouse (pmel-1) whose CD8+T cells recognize an epitope derived from the self/melanoma antigen gp100. By removing endogenous IL-15 by using tumor-bearing IL-15 knockout hosts or supplementing IL-15 by means of exogenous administration, as a component of culture media or as a transgene expressed by adoptively transferred T cells, we demonstrate that IL-15 can improve the in vivo antitumor activity of adoptively transferred CD8+T cells. These results provide several avenues for improving adoptive immunotherapy of cancer in patients.</description><subject>Adoptive Transfer</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Cancer</subject><subject>CD8-Positive T-Lymphocytes - cytology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>CD8-Positive T-Lymphocytes - transplantation</subject><subject>Cells, Cultured</subject><subject>Culture media</subject><subject>Cultured cells</subject><subject>Cytokines</subject><subject>Female</subject><subject>Genes</subject><subject>gp100 Melanoma Antigen</subject><subject>Humans</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Interleukin-15 - genetics</subject><subject>Interleukin-15 - immunology</subject><subject>Interleukin-15 - pharmacology</subject><subject>Interleukin-2 - immunology</subject><subject>Interleukin-2 - pharmacology</subject><subject>Melanoma, Experimental - immunology</subject><subject>Membrane Glycoproteins - immunology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Neoplasm Proteins - immunology</subject><subject>Receptors</subject><subject>Receptors, Antigen, T-Cell - genetics</subject><subject>Receptors, Antigen, T-Cell - immunology</subject><subject>Rodents</subject><subject>Splenocytes</subject><subject>T cell receptors</subject><subject>T lymphocytes</subject><subject>Tumors</subject><subject>Vaccination</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUGP0zAQhS0EYsvCmQtCFgc4oOzO2HEcHzhUZYEVlZBQOVuu41BXaVxsp2L_PYlabRcOnGY0873RzDxCXiJcIUh-ve9NugIOkqkaAR-RGYLCoioVPCYzACaLumTlBXmW0hYAlKjhKbnAUlYMq2pGvt4uCxT0pt-Y3rpE88ZR39ODPwQ677PPwy5EOrfZH3y-o6Glq6lSfHdmqjm6-Fi_X9GF67r0nDxpTZfci1O8JD8-3awWX4rlt8-3i_mysIKrXCjWONc4VAacaZ1qZdk0Euu64oqtxwxKBCvWgjdWGFUqwy0ra2GcbQxjil-SD8e5-2G9c411fY6m0_vodybe6WC8_rvT-43-GQ6aCwm8GvVvT_oYfg0uZb3zyY4XmN6FIekaUAIqHME3_4DbMMR-vE0zQA7IxARdHyEbQ0rRtfeLIOjJJD2ZpM8mjYrXD_c_8ydXHgCT8jwOtdSoqukD7_4L6Hbouux-55F8dSS3KYd4j3IukUvF_wCIKa28</recordid><startdate>20040217</startdate><enddate>20040217</enddate><creator>Klebanoff, Christopher A.</creator><creator>Finkelstein, Steven E.</creator><creator>Surman, Deborah R.</creator><creator>Lichtman, Michael K.</creator><creator>Gattinoni, Luca</creator><creator>Theoret, Marc R.</creator><creator>Grewal, Navrose</creator><creator>Spiess, Paul J.</creator><creator>Antony, Paul A.</creator><creator>Palmer, Douglas C.</creator><creator>Tagaya, Yutaka</creator><creator>Rosenberg, Steven A.</creator><creator>Waldmann, Thomas A.</creator><creator>Restifo, Nicholas P.</creator><general>National Academy of Sciences</general><general>National Acad 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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20040217</creationdate><title>IL-15 Enhances the in vivo Antitumor Activity of Tumor-Reactive CD8+T Cells</title><author>Klebanoff, Christopher A. ; Finkelstein, Steven E. ; Surman, Deborah R. ; Lichtman, Michael K. ; Gattinoni, Luca ; Theoret, Marc R. ; Grewal, Navrose ; Spiess, Paul J. ; Antony, Paul A. ; Palmer, Douglas C. ; Tagaya, Yutaka ; Rosenberg, Steven A. ; Waldmann, Thomas A. ; Restifo, Nicholas P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-92deede19a0eafe9f74dd71886392bd710410c5b53dc5a949a3c2485aecda2293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adoptive Transfer</topic><topic>Animals</topic><topic>Biological Sciences</topic><topic>Cancer</topic><topic>CD8-Positive T-Lymphocytes - 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However, whereas IL-2 can promote apoptosis and limit CD8+memory T cell survival and proliferation, IL-15 helps maintain a memory CD8+T cell population and can inhibit apoptosis. We sought to determine whether IL-15 could enhance the in vivo function of tumor/self-reactive CD8+T cells by using a T cell receptor transgenic mouse (pmel-1) whose CD8+T cells recognize an epitope derived from the self/melanoma antigen gp100. By removing endogenous IL-15 by using tumor-bearing IL-15 knockout hosts or supplementing IL-15 by means of exogenous administration, as a component of culture media or as a transgene expressed by adoptively transferred T cells, we demonstrate that IL-15 can improve the in vivo antitumor activity of adoptively transferred CD8+T cells. These results provide several avenues for improving adoptive immunotherapy of cancer in patients.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>14762166</pmid><doi>10.1073/pnas.0307298101</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adoptive Transfer Animals Biological Sciences Cancer CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - transplantation Cells, Cultured Culture media Cultured cells Cytokines Female Genes gp100 Melanoma Antigen Humans Immunology Immunotherapy Interleukin-15 - genetics Interleukin-15 - immunology Interleukin-15 - pharmacology Interleukin-2 - immunology Interleukin-2 - pharmacology Melanoma, Experimental - immunology Membrane Glycoproteins - immunology Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Neoplasm Proteins - immunology Receptors Receptors, Antigen, T-Cell - genetics Receptors, Antigen, T-Cell - immunology Rodents Splenocytes T cell receptors T lymphocytes Tumors Vaccination |
| title | IL-15 Enhances the in vivo Antitumor Activity of Tumor-Reactive CD8+T Cells |
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