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Clinical Studies

Natural Human Plasmacytoid Dendritic Cells Induce Antigen-Specific T-Cell Responses in Melanoma Patients

Jurjen Tel, Erik H.J.G. Aarntzen, Tetsuro Baba, Gerty Schreibelt, Barbara M. Schulte, Daniel Benitez-Ribas, Otto C. Boerman, Sandra Croockewit, Wim J.G. Oyen, Michelle van Rossum, Gregor Winkels, Pierre G. Coulie, Cornelis J.A. Punt, Carl G. Figdor and I. Jolanda M. de Vries
Jurjen Tel
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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Erik H.J.G. Aarntzen
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, GermanyAuthors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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Tetsuro Baba
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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Gerty Schreibelt
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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Barbara M. Schulte
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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Daniel Benitez-Ribas
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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Otto C. Boerman
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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Sandra Croockewit
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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Wim J.G. Oyen
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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Michelle van Rossum
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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Gregor Winkels
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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Pierre G. Coulie
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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Cornelis J.A. Punt
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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Carl G. Figdor
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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I. Jolanda M. de Vries
Authors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, GermanyAuthors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, GermanyAuthors' Affiliations: Departments of Tumor Immunology, Medical Oncology, Pediatric Oncology, Dermatology, Nuclear Medicine, and Hematology, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
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DOI: 10.1158/0008-5472.CAN-12-2583 Published February 2013
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Abstract

Vaccination against cancer by using dendritic cells has for more than a decade been based on dendritic cells generated ex vivo from monocytes or CD34+ progenitors. Here, we report on the first clinical study of therapeutic vaccination against cancer using naturally occurring plasmacytoid dendritic cells (pDC). Fifteen patients with metastatic melanoma received intranodal injections of pDCs activated and loaded with tumor antigen-associated peptides ex vivo. In vivo imaging showed that administered pDCs migrated and distributed over multiple lymph nodes. Several patients mounted antivaccine CD4+ and CD8+ T-cell responses. Despite the limited number of administered pDCs, an IFN signature was observed after each vaccination. These results indicate that vaccination with naturally occurring pDC is feasible with minimal toxicity and that in patients with metastatic melanoma, it induces favorable immune responses. Cancer Res; 73(3); 1063–75. ©2012 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received July 2, 2012.
  • Revision received November 19, 2012.
  • Accepted December 2, 2012.
  • ©2012 American Association for Cancer Research.
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Cancer Research: 73 (3)
February 2013
Volume 73, Issue 3
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Natural Human Plasmacytoid Dendritic Cells Induce Antigen-Specific T-Cell Responses in Melanoma Patients
Jurjen Tel, Erik H.J.G. Aarntzen, Tetsuro Baba, Gerty Schreibelt, Barbara M. Schulte, Daniel Benitez-Ribas, Otto C. Boerman, Sandra Croockewit, Wim J.G. Oyen, Michelle van Rossum, Gregor Winkels, Pierre G. Coulie, Cornelis J.A. Punt, Carl G. Figdor and I. Jolanda M. de Vries
Cancer Res February 1 2013 (73) (3) 1063-1075; DOI: 10.1158/0008-5472.CAN-12-2583

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Natural Human Plasmacytoid Dendritic Cells Induce Antigen-Specific T-Cell Responses in Melanoma Patients
Jurjen Tel, Erik H.J.G. Aarntzen, Tetsuro Baba, Gerty Schreibelt, Barbara M. Schulte, Daniel Benitez-Ribas, Otto C. Boerman, Sandra Croockewit, Wim J.G. Oyen, Michelle van Rossum, Gregor Winkels, Pierre G. Coulie, Cornelis J.A. Punt, Carl G. Figdor and I. Jolanda M. de Vries
Cancer Res February 1 2013 (73) (3) 1063-1075; DOI: 10.1158/0008-5472.CAN-12-2583
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