Vaccination with Irradiated Autologous Melanoma Cells Engineered to Secrete Human Granulocyte--Macrophage Colony-Stimulating Factor Generates Potent Antitumor Immunity in Patients with Metastatic Melanoma
We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte--macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1998-10, Vol.95 (22), p.13141-13146 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 95 |
| creator | Soiffer, Robert Lynch, Thomas Mihm, Martin Jung, Ken Rhuda, Catherine Schmollinger, Jan C. Hodi, F. Stephen Liebster, Laura Lam, Prudence Mentzer, Steven Singer, Samuel Tanabe, Kenneth K. Cosimi, A. Benedict Duda, Rosemary Sober, Arthur Bhan, Atul Daley, John Neuberg, Donna Parry, Gordon Rokovich, Joseph Richards, Laurie Drayer, Jan Berns, Anton Clift, Shirley Cohen, Lawrence K. Mulligan, Richard C. Dranoff, Glenn |
| description | We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte--macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte--macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma. |
| doi_str_mv | 10.1073/pnas.95.22.13141 |
| format | Article |
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Stephen ; Liebster, Laura ; Lam, Prudence ; Mentzer, Steven ; Singer, Samuel ; Tanabe, Kenneth K. ; Cosimi, A. Benedict ; Duda, Rosemary ; Sober, Arthur ; Bhan, Atul ; Daley, John ; Neuberg, Donna ; Parry, Gordon ; Rokovich, Joseph ; Richards, Laurie ; Drayer, Jan ; Berns, Anton ; Clift, Shirley ; Cohen, Lawrence K. ; Mulligan, Richard C. ; Dranoff, Glenn</creator><creatorcontrib>Soiffer, Robert ; Lynch, Thomas ; Mihm, Martin ; Jung, Ken ; Rhuda, Catherine ; Schmollinger, Jan C. ; Hodi, F. Stephen ; Liebster, Laura ; Lam, Prudence ; Mentzer, Steven ; Singer, Samuel ; Tanabe, Kenneth K. ; Cosimi, A. Benedict ; Duda, Rosemary ; Sober, Arthur ; Bhan, Atul ; Daley, John ; Neuberg, Donna ; Parry, Gordon ; Rokovich, Joseph ; Richards, Laurie ; Drayer, Jan ; Berns, Anton ; Clift, Shirley ; Cohen, Lawrence K. ; Mulligan, Richard C. ; Dranoff, Glenn</creatorcontrib><description>We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte--macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte--macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.95.22.13141</identifier><identifier>PMID: 9789055</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Biological Sciences ; Cancer ; Cancer Vaccines - adverse effects ; Cytokines - biosynthesis ; Cytokines - blood ; Dendritic Cells - immunology ; Dendritic Cells - pathology ; Eosinophils ; Eosinophils - immunology ; Eosinophils - pathology ; Genetic Engineering ; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis ; Granulocyte-Macrophage Colony-Stimulating Factor - genetics ; Humans ; Hypersensitivity, Delayed ; Immunization ; Immunology ; Lesions ; Lymphocytes ; Lymphocytes - immunology ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - pathology ; Macrophages - immunology ; Macrophages - pathology ; Melanoma ; Melanoma - immunology ; Melanoma - pathology ; Melanoma - therapy ; Metastasis ; Neoplasm Metastasis ; Plasma cells ; T lymphocytes ; T-Lymphocytes - immunology ; T-Lymphocytes - pathology ; Transplantation, Autologous ; Tumors ; Vaccination ; Vaccines</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1998-10, Vol.95 (22), p.13141-13146</ispartof><rights>Copyright 1993-1998 National Academy of Sciences</rights><rights>Copyright National Academy of Sciences Oct 27, 1998</rights><rights>Copyright © 1998, The National Academy of Sciences 1998</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c523t-d6ab00aadbdf16abacff12c114f3094f00dc68efb7f4064a43fef7ec4b33d9fd3</citedby><cites>FETCH-LOGICAL-c523t-d6ab00aadbdf16abacff12c114f3094f00dc68efb7f4064a43fef7ec4b33d9fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/95/22.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/46209$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/46209$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9789055$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Soiffer, Robert</creatorcontrib><creatorcontrib>Lynch, Thomas</creatorcontrib><creatorcontrib>Mihm, Martin</creatorcontrib><creatorcontrib>Jung, Ken</creatorcontrib><creatorcontrib>Rhuda, Catherine</creatorcontrib><creatorcontrib>Schmollinger, Jan C.</creatorcontrib><creatorcontrib>Hodi, F. Stephen</creatorcontrib><creatorcontrib>Liebster, Laura</creatorcontrib><creatorcontrib>Lam, Prudence</creatorcontrib><creatorcontrib>Mentzer, Steven</creatorcontrib><creatorcontrib>Singer, Samuel</creatorcontrib><creatorcontrib>Tanabe, Kenneth K.</creatorcontrib><creatorcontrib>Cosimi, A. Benedict</creatorcontrib><creatorcontrib>Duda, Rosemary</creatorcontrib><creatorcontrib>Sober, Arthur</creatorcontrib><creatorcontrib>Bhan, Atul</creatorcontrib><creatorcontrib>Daley, John</creatorcontrib><creatorcontrib>Neuberg, Donna</creatorcontrib><creatorcontrib>Parry, Gordon</creatorcontrib><creatorcontrib>Rokovich, Joseph</creatorcontrib><creatorcontrib>Richards, Laurie</creatorcontrib><creatorcontrib>Drayer, Jan</creatorcontrib><creatorcontrib>Berns, Anton</creatorcontrib><creatorcontrib>Clift, Shirley</creatorcontrib><creatorcontrib>Cohen, Lawrence K.</creatorcontrib><creatorcontrib>Mulligan, Richard C.</creatorcontrib><creatorcontrib>Dranoff, Glenn</creatorcontrib><title>Vaccination with Irradiated Autologous Melanoma Cells Engineered to Secrete Human Granulocyte--Macrophage Colony-Stimulating Factor Generates Potent Antitumor Immunity in Patients with Metastatic Melanoma</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte--macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte--macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.</description><subject>Biological Sciences</subject><subject>Cancer</subject><subject>Cancer Vaccines - adverse effects</subject><subject>Cytokines - biosynthesis</subject><subject>Cytokines - blood</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - pathology</subject><subject>Eosinophils</subject><subject>Eosinophils - immunology</subject><subject>Eosinophils - pathology</subject><subject>Genetic Engineering</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - genetics</subject><subject>Humans</subject><subject>Hypersensitivity, Delayed</subject><subject>Immunization</subject><subject>Immunology</subject><subject>Lesions</subject><subject>Lymphocytes</subject><subject>Lymphocytes - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - pathology</subject><subject>Macrophages - immunology</subject><subject>Macrophages - pathology</subject><subject>Melanoma</subject><subject>Melanoma - immunology</subject><subject>Melanoma - pathology</subject><subject>Melanoma - therapy</subject><subject>Metastasis</subject><subject>Neoplasm Metastasis</subject><subject>Plasma cells</subject><subject>T lymphocytes</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - pathology</subject><subject>Transplantation, Autologous</subject><subject>Tumors</subject><subject>Vaccination</subject><subject>Vaccines</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktvEzEUhUcIVNLCHiEhLBaIzQS_5iWxiaI2jdSISgW2luO5ThzN2KntgeY_8qNwSBQeC1jZ8vnO9fX1ybIXBI8Jrtj7rZVh3BRjSseEEU4eZSOCG5KXvMGPsxHGtMprTvnT7DyEDca4KWp8lp01Vd3gohhl379IpYyV0TiLvpm4RnPvZWtkhBZNhug6t3JDQAvopHW9RFPouoAu7cpYAJ-g6NAdKA8R0PXQS4tmXtqhc2oXIc8XUnm3XcsVoGmqZXf5XTT90KUL7QpdSRWdRzOw4NONAd26CDaiiY0mDn2S5n0_WBN3yFh0m0xJDYc-FxBliOlInZp7lj3Rsgvw_LheZJ-vLj9Nr_Obj7P5dHKTq4KymLelXGIsZbtsNUl7qbQmVBHCNcMN1xi3qqxBLyvNccklZxp0BYovGWsb3bKL7MOh7nZY9tCq1JSXndh600u_E04a8adizVqs3FdBWcXqZH97tHt3P0CIojdBpblKC2nWokr_VOHy_yCpCC-akiTwzV_gxg3ephkIigkraF1UCcIHKP1ICB70qWGCxT5NYp8m0RSCUvEzTcny6veHngzH-CT93VHfO0_qrwpCD10X4SEm9PW_0US8PBCbkEJxQnhJccN-AHo_710</recordid><startdate>19981027</startdate><enddate>19981027</enddate><creator>Soiffer, Robert</creator><creator>Lynch, Thomas</creator><creator>Mihm, Martin</creator><creator>Jung, Ken</creator><creator>Rhuda, Catherine</creator><creator>Schmollinger, Jan C.</creator><creator>Hodi, F. 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These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte--macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>9789055</pmid><doi>10.1073/pnas.95.22.13141</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1998-10, Vol.95 (22), p.13141-13146 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_jstor_primary_46209 |
| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Biological Sciences Cancer Cancer Vaccines - adverse effects Cytokines - biosynthesis Cytokines - blood Dendritic Cells - immunology Dendritic Cells - pathology Eosinophils Eosinophils - immunology Eosinophils - pathology Genetic Engineering Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis Granulocyte-Macrophage Colony-Stimulating Factor - genetics Humans Hypersensitivity, Delayed Immunization Immunology Lesions Lymphocytes Lymphocytes - immunology Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - pathology Macrophages - immunology Macrophages - pathology Melanoma Melanoma - immunology Melanoma - pathology Melanoma - therapy Metastasis Neoplasm Metastasis Plasma cells T lymphocytes T-Lymphocytes - immunology T-Lymphocytes - pathology Transplantation, Autologous Tumors Vaccination Vaccines |
| title | Vaccination with Irradiated Autologous Melanoma Cells Engineered to Secrete Human Granulocyte--Macrophage Colony-Stimulating Factor Generates Potent Antitumor Immunity in Patients with Metastatic Melanoma |
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