Autoimmune B-cell lymphopenia after successful adoptive therapy with telomerase-specific T lymphocytes
Telomerase reverse transcriptase (TERT) is a good candidate for cancer immunotherapy because it is overexpressed in 85% of all human tumors and implicated in maintenance of the transformed phenotype. TERT-based cancer vaccines have been shown to be safe, not inducing any immune-related pathology, bu...
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Veröffentlicht in: | Blood 2010-02, Vol.115 (7), p.1374-1384 |
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creator | Ugel, Stefano Scarselli, Elisa Iezzi, Manuela Mennuni, Carmela Pannellini, Tania Calvaruso, Francesco Cipriani, Barbara De Palma, Raffaele Ricci-Vitiani, Lucia Peranzoni, Elisa Musiani, Piero Zanovello, Paola Bronte, Vincenzo |
description | Telomerase reverse transcriptase (TERT) is a good candidate for cancer immunotherapy because it is overexpressed in 85% of all human tumors and implicated in maintenance of the transformed phenotype. TERT-based cancer vaccines have been shown to be safe, not inducing any immune-related pathology, but their impact on tumor progression is modest. Here we show that adoptive cell therapy with the use of high-avidity T lymphocytes reactive against telomerase can control the growth of different established tumors. Moreover, in transgenic adenocarcinoma mouse prostate mice, which develop prostate cancer, TERT-based adoptive cell therapy halted the progression to more aggressive and poorly differentiated tumors, significantly prolonging mouse survival. We also demonstrated that human tumors, including Burkitt lymphoma, and human cancer stem cells, are targeted in vivo by TERT-specific cytotoxic T lymphocytes. Effective therapy with T cells against telomerase, different from active vaccination, however, led to autoimmunity marked by a consistent, although transient, B-cell depletion in primary and secondary lymphoid organs, associated with alteration of the spleen cytoarchitecture. These results indicate B cells as an in vivo target of TERT-specific cytotoxic T lymphocytes during successful immunotherapy. |
doi_str_mv | 10.1182/blood-2009-07-233270 |
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TERT-based cancer vaccines have been shown to be safe, not inducing any immune-related pathology, but their impact on tumor progression is modest. Here we show that adoptive cell therapy with the use of high-avidity T lymphocytes reactive against telomerase can control the growth of different established tumors. Moreover, in transgenic adenocarcinoma mouse prostate mice, which develop prostate cancer, TERT-based adoptive cell therapy halted the progression to more aggressive and poorly differentiated tumors, significantly prolonging mouse survival. We also demonstrated that human tumors, including Burkitt lymphoma, and human cancer stem cells, are targeted in vivo by TERT-specific cytotoxic T lymphocytes. Effective therapy with T cells against telomerase, different from active vaccination, however, led to autoimmunity marked by a consistent, although transient, B-cell depletion in primary and secondary lymphoid organs, associated with alteration of the spleen cytoarchitecture. These results indicate B cells as an in vivo target of TERT-specific cytotoxic T lymphocytes during successful immunotherapy.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2009-07-233270</identifier><identifier>PMID: 19903903</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Adenocarcinoma - immunology ; Adenocarcinoma - therapy ; Adoptive Transfer - methods ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Applied cell therapy and gene therapy ; B-Lymphocytes - immunology ; B-Lymphocytes - pathology ; Biological and medical sciences ; Bone Marrow Cells - pathology ; Cancer Vaccines ; Cell Line, Tumor ; Colonic Neoplasms ; Disease Models, Animal ; Hematologic and hematopoietic diseases ; HLA-A2 Antigen - genetics ; HLA-A2 Antigen - immunology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Lung Neoplasms ; Lymphopenia - pathology ; Male ; Medical sciences ; Melanoma ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neoplasm Transplantation ; Prostatic Neoplasms - immunology ; Prostatic Neoplasms - therapy ; Skin Neoplasms ; Spleen - pathology ; T-Lymphocytes - immunology ; T-Lymphocytes - transplantation ; Telomerase - immunology ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><ispartof>Blood, 2010-02, Vol.115 (7), p.1374-1384</ispartof><rights>2010 American Society of Hematology</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-1dcf97628d47c705e3034a5037a22317ab454e6704fd6583e0abc8143a4f30783</citedby><cites>FETCH-LOGICAL-c437t-1dcf97628d47c705e3034a5037a22317ab454e6704fd6583e0abc8143a4f30783</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22446273$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19903903$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ugel, Stefano</creatorcontrib><creatorcontrib>Scarselli, Elisa</creatorcontrib><creatorcontrib>Iezzi, Manuela</creatorcontrib><creatorcontrib>Mennuni, Carmela</creatorcontrib><creatorcontrib>Pannellini, Tania</creatorcontrib><creatorcontrib>Calvaruso, Francesco</creatorcontrib><creatorcontrib>Cipriani, Barbara</creatorcontrib><creatorcontrib>De Palma, Raffaele</creatorcontrib><creatorcontrib>Ricci-Vitiani, Lucia</creatorcontrib><creatorcontrib>Peranzoni, Elisa</creatorcontrib><creatorcontrib>Musiani, Piero</creatorcontrib><creatorcontrib>Zanovello, Paola</creatorcontrib><creatorcontrib>Bronte, Vincenzo</creatorcontrib><title>Autoimmune B-cell lymphopenia after successful adoptive therapy with telomerase-specific T lymphocytes</title><title>Blood</title><addtitle>Blood</addtitle><description>Telomerase reverse transcriptase (TERT) is a good candidate for cancer immunotherapy because it is overexpressed in 85% of all human tumors and implicated in maintenance of the transformed phenotype. TERT-based cancer vaccines have been shown to be safe, not inducing any immune-related pathology, but their impact on tumor progression is modest. Here we show that adoptive cell therapy with the use of high-avidity T lymphocytes reactive against telomerase can control the growth of different established tumors. Moreover, in transgenic adenocarcinoma mouse prostate mice, which develop prostate cancer, TERT-based adoptive cell therapy halted the progression to more aggressive and poorly differentiated tumors, significantly prolonging mouse survival. We also demonstrated that human tumors, including Burkitt lymphoma, and human cancer stem cells, are targeted in vivo by TERT-specific cytotoxic T lymphocytes. Effective therapy with T cells against telomerase, different from active vaccination, however, led to autoimmunity marked by a consistent, although transient, B-cell depletion in primary and secondary lymphoid organs, associated with alteration of the spleen cytoarchitecture. These results indicate B cells as an in vivo target of TERT-specific cytotoxic T lymphocytes during successful immunotherapy.</description><subject>Adenocarcinoma - immunology</subject><subject>Adenocarcinoma - therapy</subject><subject>Adoptive Transfer - methods</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Applied cell therapy and gene therapy</subject><subject>B-Lymphocytes - immunology</subject><subject>B-Lymphocytes - pathology</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow Cells - pathology</subject><subject>Cancer Vaccines</subject><subject>Cell Line, Tumor</subject><subject>Colonic Neoplasms</subject><subject>Disease Models, Animal</subject><subject>Hematologic and hematopoietic diseases</subject><subject>HLA-A2 Antigen - genetics</subject><subject>HLA-A2 Antigen - immunology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Lung Neoplasms</subject><subject>Lymphopenia - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Melanoma</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Neoplasm Transplantation</subject><subject>Prostatic Neoplasms - immunology</subject><subject>Prostatic Neoplasms - therapy</subject><subject>Skin Neoplasms</subject><subject>Spleen - pathology</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - transplantation</subject><subject>Telomerase - immunology</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtr3DAQgEVpaLZJ_0EJupSelIwetuxLIA19BAK5JGehlUesim05kpyw_77erklvhYFh4JvXR8hnDpecN-Jq28fYMQHQMtBMSCk0vCMbXomGAQh4TzYAUDPVan5KPub8G4ArKaoP5JS3LcglNsTfzCWGYZhHpN-Yw76n_X6YdnHCMVhqfcFE8-wc5uznntouTiW8IC07THba09dQdrRgH4elzsjyhC744OjjOsjtC-ZzcuJtn_HTms_I04_vj7e_2P3Dz7vbm3vmlNSF8c75Vtei6ZR2GiqUIJWtQGorhOTablWlsNagfFdXjUSwW9csX1nlJehGnpGvx7lTis8z5mKGkA9f2RHjnI2WsuFc1nwh1ZF0Keac0JsphcGmveFgDoLNX8HmINiANkfBS9vFumDeDtj9a1qNLsCXFbDZ2d4nO7qQ3zghlKqFPnDXRw4XHS8Bk8ku4OiwCwldMV0M_7_kD0I2mmI</recordid><startdate>20100218</startdate><enddate>20100218</enddate><creator>Ugel, Stefano</creator><creator>Scarselli, Elisa</creator><creator>Iezzi, Manuela</creator><creator>Mennuni, Carmela</creator><creator>Pannellini, Tania</creator><creator>Calvaruso, Francesco</creator><creator>Cipriani, Barbara</creator><creator>De Palma, Raffaele</creator><creator>Ricci-Vitiani, Lucia</creator><creator>Peranzoni, Elisa</creator><creator>Musiani, Piero</creator><creator>Zanovello, Paola</creator><creator>Bronte, Vincenzo</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><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>7X8</scope></search><sort><creationdate>20100218</creationdate><title>Autoimmune B-cell lymphopenia after successful adoptive therapy with telomerase-specific T lymphocytes</title><author>Ugel, Stefano ; Scarselli, Elisa ; Iezzi, Manuela ; Mennuni, Carmela ; Pannellini, Tania ; Calvaruso, Francesco ; Cipriani, Barbara ; De Palma, Raffaele ; Ricci-Vitiani, Lucia ; Peranzoni, Elisa ; Musiani, Piero ; Zanovello, Paola ; Bronte, Vincenzo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-1dcf97628d47c705e3034a5037a22317ab454e6704fd6583e0abc8143a4f30783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adenocarcinoma - immunology</topic><topic>Adenocarcinoma - therapy</topic><topic>Adoptive Transfer - methods</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Applied cell therapy and gene therapy</topic><topic>B-Lymphocytes - immunology</topic><topic>B-Lymphocytes - pathology</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow Cells - pathology</topic><topic>Cancer Vaccines</topic><topic>Cell Line, Tumor</topic><topic>Colonic Neoplasms</topic><topic>Disease Models, Animal</topic><topic>Hematologic and hematopoietic diseases</topic><topic>HLA-A2 Antigen - genetics</topic><topic>HLA-A2 Antigen - immunology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Lung Neoplasms</topic><topic>Lymphopenia - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Melanoma</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Neoplasm Transplantation</topic><topic>Prostatic Neoplasms - immunology</topic><topic>Prostatic Neoplasms - therapy</topic><topic>Skin Neoplasms</topic><topic>Spleen - pathology</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - transplantation</topic><topic>Telomerase - immunology</topic><topic>Transfusions. Complications. Transfusion reactions. 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TERT-based cancer vaccines have been shown to be safe, not inducing any immune-related pathology, but their impact on tumor progression is modest. Here we show that adoptive cell therapy with the use of high-avidity T lymphocytes reactive against telomerase can control the growth of different established tumors. Moreover, in transgenic adenocarcinoma mouse prostate mice, which develop prostate cancer, TERT-based adoptive cell therapy halted the progression to more aggressive and poorly differentiated tumors, significantly prolonging mouse survival. We also demonstrated that human tumors, including Burkitt lymphoma, and human cancer stem cells, are targeted in vivo by TERT-specific cytotoxic T lymphocytes. Effective therapy with T cells against telomerase, different from active vaccination, however, led to autoimmunity marked by a consistent, although transient, B-cell depletion in primary and secondary lymphoid organs, associated with alteration of the spleen cytoarchitecture. 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subjects | Adenocarcinoma - immunology Adenocarcinoma - therapy Adoptive Transfer - methods Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Applied cell therapy and gene therapy B-Lymphocytes - immunology B-Lymphocytes - pathology Biological and medical sciences Bone Marrow Cells - pathology Cancer Vaccines Cell Line, Tumor Colonic Neoplasms Disease Models, Animal Hematologic and hematopoietic diseases HLA-A2 Antigen - genetics HLA-A2 Antigen - immunology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lung Neoplasms Lymphopenia - pathology Male Medical sciences Melanoma Mice Mice, Inbred C57BL Mice, Transgenic Neoplasm Transplantation Prostatic Neoplasms - immunology Prostatic Neoplasms - therapy Skin Neoplasms Spleen - pathology T-Lymphocytes - immunology T-Lymphocytes - transplantation Telomerase - immunology Transfusions. Complications. Transfusion reactions. Cell and gene therapy |
title | Autoimmune B-cell lymphopenia after successful adoptive therapy with telomerase-specific T lymphocytes |
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