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Blood, 1 November 2000, Vol. 96, No. 9, pp. 3102-3108

IMMUNOBIOLOGY

Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells

Peter Brossart, Stefan Wirths, Gernot Stuhler, Volker L. Reichardt, Lothar Kanz, and Wolfram Brugger

From the University of Tübingen, Department of Hematology, Oncology and Immunology, Tübingen, Germany.

Vaccination of patients with cancer using dendritic cells (DCs) was shown to be effective for B-cell lymphoma and malignant melanoma. Here we provide evidence that patients with advanced breast and ovarian cancer can be efficiently vaccinated with autologous DCs pulsed with HER-2/neu- or MUC1-derived peptides. Ten patients were included in this pilot study. The DC vaccinations were well tolerated with no side effects. In 5 of 10 patients, peptide-specific cytotoxic T lymphocytes (CTLs) could be detected in the peripheral blood using both intracellular IFN-gamma staining and 51Cr-release assays. The major CTL response in vivo was induced with the HER-2/neu-derived E75 and the MUC1-derived M1.2 peptide, which lasted for more than 6 months, suggesting that these peptides might be immunodominant. In addition, in one patient vaccinated with the MUC1-derived peptides, CEA- and MAGE-3 peptide-specific T-cell responses were detected after several vaccinations. In a second patient immunized with the HER-2/neu peptides, MUC1-specific T lymphocytes were induced after 7 immunizations, suggesting that antigen spreading in vivo might occur after successful immunization with a single tumor antigen. Our results show that vaccination of DCs pulsed with a single tumor antigen may induce immunologic responses in patients with breast and ovarian cancer. This study may be relevant to the design of future clinical trials of other peptide-based vaccines.

© 2000 by The American Society of Hematology.
 

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Expansion of dendritic cell precursors from human CD34+ progenitor cells isolated from healthy donor blood; growth factor combination determines proliferation rate and functional outcome
J. Leukoc. Biol., August 1, 2002; 72(2): 321 - 329.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
R. Spisek, P. Chevallier, N. Morineau, N. Milpied, H. Avet-Loiseau, J.-L. Harousseau, K. Meflah, and M. Gregoire
Induction of Leukemia-specific Cytotoxic Response by Cross-Presentation of Late-Apoptotic Leukemic Blasts by Autologous Dendritic Cells of Nonleukemic Origin
Cancer Res., May 1, 2002; 62(10): 2861 - 2868.
[Abstract] [Full Text] [PDF]


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Physiol. Rev.Home page
M. F. Lipscomb and B. J. Masten
Dendritic Cells: Immune Regulators in Health and Disease
Physiol Rev, January 1, 2002; 82(1): 97 - 130.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
T. D. Schell and S. S. Tevethia
Control of Advanced Choroid Plexus Tumors in SV40 T Antigen Transgenic Mice Following Priming of Donor CD8+ T Lymphocytes by the Endogenous Tumor Antigen
J. Immunol., December 15, 2001; 167(12): 6947 - 6956.
[Abstract] [Full Text] [PDF]


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J. Leukoc. Biol.Home page
K. Kato, Y. Takaue, and H. Wakasugi
T-cell-conditioned medium efficiently induces the maturation and function of human dendritic cells
J. Leukoc. Biol., December 1, 2001; 70(6): 941 - 949.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
P. Brossart, A. Schneider, P. Dill, T. Schammann, F. Grunebach, S. Wirths, L. Kanz, H.-J. Buhring, and W. Brugger
The Epithelial Tumor Antigen MUC1 Is Expressed in Hematological Malignancies and Is Recognized by MUC1-specific Cytotoxic T-Lymphocytes
Cancer Res., September 1, 2001; 61(18): 6846 - 6850.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
C. Meyer zum Buschenfelde, J. Metzger, C. Hermann, N. Nicklisch, C. Peschel, and H. Bernhard
The Generation of Both T Killer and Th Cell Clones Specific for the Tumor-Associated Antigen HER2 Using Retrovirally Transduced Dendritic Cells
J. Immunol., August 1, 2001; 167(3): 1712 - 1719.
[Abstract] [Full Text] [PDF]



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