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[Cancer Research 61, 5850-5856, August 1, 2001]
© 2001 American Association for Cancer Research

Immunology

Heterogeneous T-Cell Response to MAGE-A10254–262

High Avidity-specific Cytolytic T Lymphocytes Show Superior Antitumor Activity1

Valérie Dutoit, Verena Rubio-Godoy, Pierre-Yves Dietrich, Anne-Lise Quiqueres, Valérie Schnuriger, Donata Rimoldi, Danielle Liénard, Daniel Speiser, Philippe Guillaume, Pascal Batard, Jean-Charles Cerottini, Pedro Romero and Danila Valmori2

Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne [V. D., V. R-G., D. L., D. S., P. B., J-C. C., P. R., D. V.]; Division of Oncology, Laboratory of Tumor Immunology, University Hospital, 1211 Geneva 14 [P-Y. D., A-L. Q., V. S.]; Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges [D. R., P. G., J-C. C.]; and Multidisciplinary Oncology Center, University Hospital, 1011 Lausanne [D. L.], Switzerland

MAGE-encoded antigens, which are expressed by tumors of many histological types but not in normal tissues, are suitable candidates for vaccine-based immunotherapy of cancers. Thus far, however, T-cell responses to MAGE antigens have been detected only occasionally in cancer patients. In contrast, by using HLA/peptide fluorescent tetramers, we have observed recently that CD8+ T cells specific for peptide MAGE-A10254–262 can be detected frequently in peptide-stimulated peripheral blood mononuclear cells from HLA-A2-expressing melanoma patients and healthy donors. On the basis of these results, antitumoral vaccination trials using peptide MAGE-A10254–262 have been implemented recently. In the present study, we have characterized MAGE-A10254–262-specific CD8+ T cells in polyclonal cultures and at the clonal level. The results indicate that the repertoire of MAGE-A10254–262-specific CD8+ T cells is diverse both in terms of clonal composition, efficiency of peptide recognition, and tumor-specific lytic activity. Importantly, only CD8+ T cells able to recognize the antigenic peptide with high efficiency are able to lyse MAGE-A10-expressing tumor cells. Under defined experimental conditions, the tetramer staining intensity exhibited by MAGE-A10254–262-specific CD8+ T cells correlates with efficiency of peptide recognition so that "high" and "low" avidity cells can be separated by FACS. Altogether, the data reported here provide evidence for functional diversity of MAGE-A10254–262-specific T cells and will be instrumental for the monitoring of peptide MAGE-A10254–262-based clinical trials.




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Molecular Cancer Research Cancer Prevention Research
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Copyright © 2001 by the American Association for Cancer Research.