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The Journal of Immunology, 2008, 180: 3585-3593.
Copyright © 2008 by The American Association of Immunologists, Inc.

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Vaccination of a Melanoma Patient with Mature Dendritic Cells Pulsed with MAGE-3 Peptides Triggers the Activity of Nonvaccine Anti-Tumor Cells1

Javier Carrasco2,*, Aline Van Pel*, Bart Neyns{dagger}, Bernard Lethé*, Francis Brasseur*, Nicolina Renkvist*, Pierre van der Bruggen*, Nicolas van Baren*, Robert Paulus§, Kris Thielemans{ddagger}, Thierry Boon* and Danièle Godelaine3,*

* Ludwig Institute for Cancer Research, Christian de Duve Institute, Cellular Genetics Unit, Université Catholique de Louvain; {dagger} Department of Medical Oncology, Universitair Ziekenhuis Brussel; {ddagger} Department of Physiology-Immunology, Faculty of Medicine, Vrije Universiteit Brussel, Brussels; and § Centre hospitalier Peltzer-La Tourelle, Verviers, Belgium

We previously characterized the CTL response of a melanoma patient who experienced tumor regression following vaccination with an ALVAC virus coding for a MAGE-A3 Ag. Whereas anti-vaccine CTL were rare in the blood and inside metastases of this patient, anti-tumor CTL recognizing other tumor Ags, mainly MAGE-C2, were 100 times more frequent in the blood and considerably enriched in metastases following vaccination. In this study we report the analysis of the CTL response of a second melanoma patient who showed a mixed tumor response after vaccination with dendritic cells pulsed with two MAGE-A3 antigenic peptides presented, respectively, by HLA-A1 and HLA-DP4. Anti-MAGE-3.A1 CD8 and anti-MAGE-3.DP4 CD4 T cells became detectable in the blood after vaccination at a frequency of ~10–5 among the CD8 or CD4 T cells, respectively, and they were slightly enriched in slowly progressing metastases. Additional anti-tumor CTL were present in the blood at a frequency of 2 x 10–4 among the CD8 T cells and, among these, an anti-MAGE-C2 CTL clone was detected only following vaccination and was enriched by >1,000-fold in metastases relative to the blood. The striking similarity of these results with our previous observations further supports the hypothesis that the induction of a few anti-vaccine T cells may prime or restimulate additional anti-tumor T cell clones that are mainly responsible for the tumor regression.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by grants from the Fédération Belge contre le Cancer (Belgium), the Fonds de la Recherche Scientifique Médicale (Belgium), and the Fonds National de la Recherche Scientifique (Belgium). J.C. was supported by a Télévie Grant from the Fonds National de la Recherche Scientifique (Belgium), and N.R. was supported by a fellowship obtained from the Marie Curie Organization.

2 Current address: Hôpitaux Saint-Joseph, Sainte-Thérèse and Institut de Médecine, Traumatologie et Réadaptation, Department of Medicine-Oncology, Rue de la Duchère 6, B-6060 Gilly, Belgium.

3 Address correspondence and reprint requests to Dr. Danièle Godelaine, Ludwig Institute for Cancer Research, avenue Hippocrate 74, Université Catholique de Louvain 7459, B-1200 Brussels, Belgium. E-mail address: daniele.godelaine{at}bru.licr.org

4 Abbreviations used in this paper: DC, dendritic cell; MLPC, mixed lymphocyte-peptide culture; TIL, tumor-infiltrating lymphocyte.




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T. Connerotte, A. Van Pel, D. Godelaine, E. Tartour, B. Schuler-Thurner, S. Lucas, K. Thielemans, G. Schuler, and P. G. Coulie
Functions of Anti-MAGE T-Cells Induced in Melanoma Patients under Different Vaccination Modalities
Cancer Res., May 15, 2008; 68(10): 3931 - 3940.
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