The Journal of Experimental Medicine
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Published online 4 December 2000.
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© The Rockefeller University Press, 0022-1007/2000/12/1535/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 11, December 4, 2000 1535-1544

Original Article

Cross-Priming of Naive Cd8 T Cells against Melanoma Antigens Using Dendritic Cells Loaded with Killed Allogeneic Melanoma Cells

Frederic Berarda, Patrick Blancoa, Jean Davousta, Eve-Marie Neidhart-Berarda, Mahyar Nouri-Shirazia, Nicolas Taqueta, Donata Rimoldib, Jean Charles Cerottinib, Jacques Banchereaua, and A. Karolina Paluckaa

a Baylor Institute for Immunology Research, Dallas, Texas 75204
b Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, University Hospital, CHUV, CH-1011 Lausanne, Switzerland
Baylor Institute for Immunology Research, 3434 Live Oak, Dallas, TX 75204.214-820-4813214-820-7450

ak.palucka{at}baylordallas.edu

The goal of tumor immunotherapy is to elicit immune responses against autologous tumors. It would be highly desirable that such responses include multiple T cell clones against multiple tumor antigens. This could be obtained using the antigen presenting capacity of dendritic cells (DCs) and cross-priming. That is, one could load the DC with tumor lines of any human histocompatibility leukocyte antigen (HLA) type to elicit T cell responses against the autologous tumor. In this study, we show that human DCs derived from monocytes and loaded with killed melanoma cells prime naive CD45RA+CD27+CD8+ T cells against the four shared melanoma antigens: MAGE-3, gp100, tyrosinase, and MART-1. HLA-A201+ naive T cells primed by DCs loaded with HLA-A201– melanoma cells are able to kill several HLA-A201+ melanoma targets. Cytotoxic T lymphocyte priming towards melanoma antigens is also obtained with cells from metastatic melanoma patients. This demonstration of cross-priming against shared tumor antigens builds the basis for using allogeneic tumor cell lines to deliver tumor antigens to DCs for vaccination protocols.

Key Words: shared tumor antigens • cross-priming • tumor immunity • tumor vaccine • immunotherapy

F. Berard and P. Blanco contributed equally to this work.

J. Davoust's present address is Institut Curie, U255, 26 rue d'Ulm, 75005 Paris, France.

Abbreviations used in this paper: BA, betulinic acid; CM, complete culture medium; DC, dendritic cell; ELISPOT, enzyme-linked immunospot; TAA, tumor-associated Ag.

© 2000 The Rockefeller University Press


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