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Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma

Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage I...

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Autores principales: Thurner, Beatrice, Haendle, Ina, Röder, Claudia, Dieckmann, Detlef, Keikavoussi, Petra, Jonuleit, Helmut, Bender, Armin, Maczek, Christian, Schreiner, Doris, von den Driesch, Peter, Bröcker, Eva B., Steinman, Ralph M., Enk, Alexander, Kämpgen, Eckhart, Schuler, Gerold
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195739/
https://www.ncbi.nlm.nih.gov/pubmed/10587357
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author Thurner, Beatrice
Haendle, Ina
Röder, Claudia
Dieckmann, Detlef
Keikavoussi, Petra
Jonuleit, Helmut
Bender, Armin
Maczek, Christian
Schreiner, Doris
von den Driesch, Peter
Bröcker, Eva B.
Steinman, Ralph M.
Enk, Alexander
Kämpgen, Eckhart
Schuler, Gerold
author_facet Thurner, Beatrice
Haendle, Ina
Röder, Claudia
Dieckmann, Detlef
Keikavoussi, Petra
Jonuleit, Helmut
Bender, Armin
Maczek, Christian
Schreiner, Doris
von den Driesch, Peter
Bröcker, Eva B.
Steinman, Ralph M.
Enk, Alexander
Kämpgen, Eckhart
Schuler, Gerold
author_sort Thurner, Beatrice
collection PubMed
description Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 × 10(6) DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 × 10(6) and 12 × 10(6) DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1–specific CD8(+) cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8(+) T cell infiltration, whereas nonregressing lesions lacked CD8(+) T cells as well as Mage-3 mRNA expression. This study proves the principle that DC “vaccines” can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8(+) CTL–tumor cell interaction in situ as well as escape by lack of tumor antigen expression.
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spelling pubmed-21957392008-04-16 Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma Thurner, Beatrice Haendle, Ina Röder, Claudia Dieckmann, Detlef Keikavoussi, Petra Jonuleit, Helmut Bender, Armin Maczek, Christian Schreiner, Doris von den Driesch, Peter Bröcker, Eva B. Steinman, Ralph M. Enk, Alexander Kämpgen, Eckhart Schuler, Gerold J Exp Med Original Article Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 × 10(6) DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 × 10(6) and 12 × 10(6) DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1–specific CD8(+) cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8(+) T cell infiltration, whereas nonregressing lesions lacked CD8(+) T cells as well as Mage-3 mRNA expression. This study proves the principle that DC “vaccines” can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8(+) CTL–tumor cell interaction in situ as well as escape by lack of tumor antigen expression. The Rockefeller University Press 1999-12-06 /pmc/articles/PMC2195739/ /pubmed/10587357 Text en © 1999 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Thurner, Beatrice
Haendle, Ina
Röder, Claudia
Dieckmann, Detlef
Keikavoussi, Petra
Jonuleit, Helmut
Bender, Armin
Maczek, Christian
Schreiner, Doris
von den Driesch, Peter
Bröcker, Eva B.
Steinman, Ralph M.
Enk, Alexander
Kämpgen, Eckhart
Schuler, Gerold
Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma
title Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma
title_full Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma
title_fullStr Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma
title_full_unstemmed Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma
title_short Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma
title_sort vaccination with mage-3a1 peptide–pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic t cells and induces regression of some metastases in advanced stage iv melanoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195739/
https://www.ncbi.nlm.nih.gov/pubmed/10587357
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