Tumor Cell Surface Expression of Granulocyte-Macrophage Colony-Stimulating Factor Elicits Antitumor Immunity and Protects from Tumor Challenge in the P815 Mouse Mastocytoma Tumor Model
A novel membrane-bound form of GM-CSF (mbGM-CSF) was expressed on the surface of the mouse mastocytoma cell line P815 to target tumor cell-associated Ags to epidermal Langerhans cells. Transfected clones stimulated the proliferation of syngeneic bone marrow cells, indicating that mbGM-CSF is biologi...
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Veröffentlicht in: | The Journal of immunology (1950) 1999-06, Vol.162 (12), p.7343-7349 |
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creator | Soo Hoo, William Lundeen, Katherine A Kohrumel, Joshua R Pham, Nhat-Long Brostoff, Steven W Bartholomew, Richard M Carlo, Dennis J |
description | A novel membrane-bound form of GM-CSF (mbGM-CSF) was expressed on the surface of the mouse mastocytoma cell line P815 to target tumor cell-associated Ags to epidermal Langerhans cells. Transfected clones stimulated the proliferation of syngeneic bone marrow cells, indicating that mbGM-CSF is biologically active. We evaluated the in vivo effects of mbGM-CSF by comparing the growth of mbGM-CSF cells (termed 1D6.1E5) to that of wild-type P815 cells in DBA/2 mice. The growth rates of tumors initiated by P815 and 1D6.1E5 were similar until day 12, after which P815 tumors grew to large sizes while 1D6. 1E5 tumors were rejected. In contrast, the growth of both tumors was unimpeded when injected into nude mice, suggesting that a T cell-dependent antitumor response was induced by 1D6.1E5 in normal mice. Lymphocytes from 1D6.1E5-vaccinated mice were able to kill 51Cr-labeled P815 cells in a dose-dependent fashion that was inhibited by anti-CD8 Abs, suggesting that the antitumor response involved CD8+ CTL. We then tested whether vaccination with these cells would elicit a protective antitumor response by injecting mice with either irradiated 1D6.1E5 or P815 cells and challenging them with nonirradiated P815 cells. 1D6.1E5-treated mice grew small tumors that soon disappeared in all animals. In contrast, the majority of animals receiving the irradiated wild-type tumor vaccine grew large tumors, and 50% died. These data demonstrate that mbGM-CSF expressed on the surface of tumor cells is biologically active and elicits protective antitumor immunity. |
doi_str_mv | 10.4049/jimmunol.162.12.7343 |
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Transfected clones stimulated the proliferation of syngeneic bone marrow cells, indicating that mbGM-CSF is biologically active. We evaluated the in vivo effects of mbGM-CSF by comparing the growth of mbGM-CSF cells (termed 1D6.1E5) to that of wild-type P815 cells in DBA/2 mice. The growth rates of tumors initiated by P815 and 1D6.1E5 were similar until day 12, after which P815 tumors grew to large sizes while 1D6. 1E5 tumors were rejected. In contrast, the growth of both tumors was unimpeded when injected into nude mice, suggesting that a T cell-dependent antitumor response was induced by 1D6.1E5 in normal mice. Lymphocytes from 1D6.1E5-vaccinated mice were able to kill 51Cr-labeled P815 cells in a dose-dependent fashion that was inhibited by anti-CD8 Abs, suggesting that the antitumor response involved CD8+ CTL. We then tested whether vaccination with these cells would elicit a protective antitumor response by injecting mice with either irradiated 1D6.1E5 or P815 cells and challenging them with nonirradiated P815 cells. 1D6.1E5-treated mice grew small tumors that soon disappeared in all animals. In contrast, the majority of animals receiving the irradiated wild-type tumor vaccine grew large tumors, and 50% died. These data demonstrate that mbGM-CSF expressed on the surface of tumor cells is biologically active and elicits protective antitumor immunity.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.162.12.7343</identifier><identifier>PMID: 10358185</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Animals ; Bone Marrow Cells - pathology ; Cancer Vaccines - immunology ; Cell Division - genetics ; Cell Division - immunology ; Cell Membrane - immunology ; Cell Membrane - metabolism ; Clone Cells - radiation effects ; Clone Cells - transplantation ; Female ; Genetic Vectors - chemical synthesis ; Graft Rejection - genetics ; Graft Rejection - immunology ; Graft Rejection - pathology ; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis ; Granulocyte-Macrophage Colony-Stimulating Factor - genetics ; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism ; Immunocompromised Host ; Mast-Cell Sarcoma - metabolism ; Mast-Cell Sarcoma - pathology ; Membrane Proteins - biosynthesis ; Membrane Proteins - genetics ; Mice ; Mice, Inbred BALB C ; Mice, Inbred DBA ; Mice, Nude ; Neoplasm Transplantation ; T-Lymphocytes, Cytotoxic - immunology ; Tumor Cells, Cultured</subject><ispartof>The Journal of immunology (1950), 1999-06, Vol.162 (12), p.7343-7349</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-b839593411ed19201264c653e99fba253c1f6d1dac05d2a755f4734df1eb8cbc3</citedby><cites>FETCH-LOGICAL-c413t-b839593411ed19201264c653e99fba253c1f6d1dac05d2a755f4734df1eb8cbc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10358185$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Soo Hoo, William</creatorcontrib><creatorcontrib>Lundeen, Katherine A</creatorcontrib><creatorcontrib>Kohrumel, Joshua R</creatorcontrib><creatorcontrib>Pham, Nhat-Long</creatorcontrib><creatorcontrib>Brostoff, Steven W</creatorcontrib><creatorcontrib>Bartholomew, Richard M</creatorcontrib><creatorcontrib>Carlo, Dennis J</creatorcontrib><title>Tumor Cell Surface Expression of Granulocyte-Macrophage Colony-Stimulating Factor Elicits Antitumor Immunity and Protects from Tumor Challenge in the P815 Mouse Mastocytoma Tumor Model</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>A novel membrane-bound form of GM-CSF (mbGM-CSF) was expressed on the surface of the mouse mastocytoma cell line P815 to target tumor cell-associated Ags to epidermal Langerhans cells. Transfected clones stimulated the proliferation of syngeneic bone marrow cells, indicating that mbGM-CSF is biologically active. We evaluated the in vivo effects of mbGM-CSF by comparing the growth of mbGM-CSF cells (termed 1D6.1E5) to that of wild-type P815 cells in DBA/2 mice. The growth rates of tumors initiated by P815 and 1D6.1E5 were similar until day 12, after which P815 tumors grew to large sizes while 1D6. 1E5 tumors were rejected. In contrast, the growth of both tumors was unimpeded when injected into nude mice, suggesting that a T cell-dependent antitumor response was induced by 1D6.1E5 in normal mice. Lymphocytes from 1D6.1E5-vaccinated mice were able to kill 51Cr-labeled P815 cells in a dose-dependent fashion that was inhibited by anti-CD8 Abs, suggesting that the antitumor response involved CD8+ CTL. We then tested whether vaccination with these cells would elicit a protective antitumor response by injecting mice with either irradiated 1D6.1E5 or P815 cells and challenging them with nonirradiated P815 cells. 1D6.1E5-treated mice grew small tumors that soon disappeared in all animals. In contrast, the majority of animals receiving the irradiated wild-type tumor vaccine grew large tumors, and 50% died. These data demonstrate that mbGM-CSF expressed on the surface of tumor cells is biologically active and elicits protective antitumor immunity.</description><subject>Animals</subject><subject>Bone Marrow Cells - pathology</subject><subject>Cancer Vaccines - immunology</subject><subject>Cell Division - genetics</subject><subject>Cell Division - immunology</subject><subject>Cell Membrane - immunology</subject><subject>Cell Membrane - metabolism</subject><subject>Clone Cells - radiation effects</subject><subject>Clone Cells - transplantation</subject><subject>Female</subject><subject>Genetic Vectors - chemical synthesis</subject><subject>Graft Rejection - genetics</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - pathology</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - genetics</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - metabolism</subject><subject>Immunocompromised Host</subject><subject>Mast-Cell Sarcoma - metabolism</subject><subject>Mast-Cell Sarcoma - pathology</subject><subject>Membrane Proteins - biosynthesis</subject><subject>Membrane Proteins - genetics</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred DBA</subject><subject>Mice, Nude</subject><subject>Neoplasm Transplantation</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Tumor Cells, Cultured</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctuGyEUhlHVqnHSvkFVsaq6GRcYYGaWkeVcpFiNlHSNGIbxEHFxgZHrN-vjFdeulF1XLPjOd47-H4BPGC0pot23F-Pc7INdYk6WmCybmtZvwAIzhirOEX8LFggRUuGGNxfgMqUXhBBHhL4HFxjVrMUtW4Dfz7MLEa60tfBpjqNUGq5_7aJOyQQPwwhvo_SzDeqQdbWRKobdJLcaroIN_lA9ZeNmK7PxW3gjVS6utTXK5ASvfTb5r_3-eKnJByj9AB9jyFqV_zEGB8_rJ2mt9kVrPMyTho8tZnAT5qThRqZ83B6cPNObMGj7AbwbpU364_m9Aj9u1s-ru-rh--396vqhUhTXuerbumNdTTHWA-4IwoRTxVmtu27sJWG1wiMf8CAVYgORDWMjLUkOI9Z9q3pVX4EvJ-8uhp-zTlk4k1SJS3pd7hO8a1FTvP8FcUMYbWhXQHoCS5YpRT2KXTROxoPASByrFf-qFaVagYk4VlvGPp_9c-_08Gro1GUBvp6AyWynvYlaJFdiLTgW-_3-tesPSbizOw</recordid><startdate>19990615</startdate><enddate>19990615</enddate><creator>Soo Hoo, William</creator><creator>Lundeen, Katherine A</creator><creator>Kohrumel, Joshua R</creator><creator>Pham, Nhat-Long</creator><creator>Brostoff, Steven W</creator><creator>Bartholomew, Richard M</creator><creator>Carlo, Dennis J</creator><general>Am Assoc Immnol</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>19990615</creationdate><title>Tumor Cell Surface Expression of Granulocyte-Macrophage Colony-Stimulating Factor Elicits Antitumor Immunity and Protects from Tumor Challenge in the P815 Mouse Mastocytoma Tumor Model</title><author>Soo Hoo, William ; Lundeen, Katherine A ; Kohrumel, Joshua R ; Pham, Nhat-Long ; Brostoff, Steven W ; Bartholomew, Richard M ; Carlo, Dennis J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-b839593411ed19201264c653e99fba253c1f6d1dac05d2a755f4734df1eb8cbc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Bone Marrow Cells - pathology</topic><topic>Cancer Vaccines - immunology</topic><topic>Cell Division - genetics</topic><topic>Cell Division - immunology</topic><topic>Cell Membrane - immunology</topic><topic>Cell Membrane - metabolism</topic><topic>Clone Cells - radiation effects</topic><topic>Clone Cells - transplantation</topic><topic>Female</topic><topic>Genetic Vectors - chemical synthesis</topic><topic>Graft Rejection - genetics</topic><topic>Graft Rejection - immunology</topic><topic>Graft Rejection - pathology</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - genetics</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - metabolism</topic><topic>Immunocompromised Host</topic><topic>Mast-Cell Sarcoma - metabolism</topic><topic>Mast-Cell Sarcoma - pathology</topic><topic>Membrane Proteins - biosynthesis</topic><topic>Membrane Proteins - genetics</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred DBA</topic><topic>Mice, Nude</topic><topic>Neoplasm Transplantation</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Soo Hoo, William</creatorcontrib><creatorcontrib>Lundeen, Katherine A</creatorcontrib><creatorcontrib>Kohrumel, Joshua R</creatorcontrib><creatorcontrib>Pham, Nhat-Long</creatorcontrib><creatorcontrib>Brostoff, Steven W</creatorcontrib><creatorcontrib>Bartholomew, Richard M</creatorcontrib><creatorcontrib>Carlo, Dennis J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Soo Hoo, William</au><au>Lundeen, Katherine A</au><au>Kohrumel, Joshua R</au><au>Pham, Nhat-Long</au><au>Brostoff, Steven W</au><au>Bartholomew, Richard M</au><au>Carlo, Dennis J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor Cell Surface Expression of Granulocyte-Macrophage Colony-Stimulating Factor Elicits Antitumor Immunity and Protects from Tumor Challenge in the P815 Mouse Mastocytoma Tumor Model</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>1999-06-15</date><risdate>1999</risdate><volume>162</volume><issue>12</issue><spage>7343</spage><epage>7349</epage><pages>7343-7349</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>A novel membrane-bound form of GM-CSF (mbGM-CSF) was expressed on the surface of the mouse mastocytoma cell line P815 to target tumor cell-associated Ags to epidermal Langerhans cells. Transfected clones stimulated the proliferation of syngeneic bone marrow cells, indicating that mbGM-CSF is biologically active. We evaluated the in vivo effects of mbGM-CSF by comparing the growth of mbGM-CSF cells (termed 1D6.1E5) to that of wild-type P815 cells in DBA/2 mice. The growth rates of tumors initiated by P815 and 1D6.1E5 were similar until day 12, after which P815 tumors grew to large sizes while 1D6. 1E5 tumors were rejected. In contrast, the growth of both tumors was unimpeded when injected into nude mice, suggesting that a T cell-dependent antitumor response was induced by 1D6.1E5 in normal mice. Lymphocytes from 1D6.1E5-vaccinated mice were able to kill 51Cr-labeled P815 cells in a dose-dependent fashion that was inhibited by anti-CD8 Abs, suggesting that the antitumor response involved CD8+ CTL. We then tested whether vaccination with these cells would elicit a protective antitumor response by injecting mice with either irradiated 1D6.1E5 or P815 cells and challenging them with nonirradiated P815 cells. 1D6.1E5-treated mice grew small tumors that soon disappeared in all animals. In contrast, the majority of animals receiving the irradiated wild-type tumor vaccine grew large tumors, and 50% died. These data demonstrate that mbGM-CSF expressed on the surface of tumor cells is biologically active and elicits protective antitumor immunity.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>10358185</pmid><doi>10.4049/jimmunol.162.12.7343</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Bone Marrow Cells - pathology Cancer Vaccines - immunology Cell Division - genetics Cell Division - immunology Cell Membrane - immunology Cell Membrane - metabolism Clone Cells - radiation effects Clone Cells - transplantation Female Genetic Vectors - chemical synthesis Graft Rejection - genetics Graft Rejection - immunology Graft Rejection - pathology Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis Granulocyte-Macrophage Colony-Stimulating Factor - genetics Granulocyte-Macrophage Colony-Stimulating Factor - metabolism Immunocompromised Host Mast-Cell Sarcoma - metabolism Mast-Cell Sarcoma - pathology Membrane Proteins - biosynthesis Membrane Proteins - genetics Mice Mice, Inbred BALB C Mice, Inbred DBA Mice, Nude Neoplasm Transplantation T-Lymphocytes, Cytotoxic - immunology Tumor Cells, Cultured |
title | Tumor Cell Surface Expression of Granulocyte-Macrophage Colony-Stimulating Factor Elicits Antitumor Immunity and Protects from Tumor Challenge in the P815 Mouse Mastocytoma Tumor Model |
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