Identification of human tumor antigens group


Pierre van der Bruggen, Member

Didier COLAU, Senior Investigator
Daniele GODELAINE, Senior Investigator
Isabelle JACQUEMART, Postdoctoral Fellow
Claude WILDMANN, Research Associate
Sabrina OTTAVIANI, Research Assistant
Nathalie DEMOTTE, Research Assistant
Violaine FRANÇOIS, PhD Student
Grégoire WIEERS, MD, PhD Student
Débora PICCOLO, Research Assistant
Vinh HA THI, Technician

P van der Bruggen





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pvdb_group

The group led by Pierre van der Bruggen has defined antigenic peptides encoded by genes such as those of the MAGE family. These peptides have been used in therapeutic vaccination trials of cancer patients and have served as tools for a reliable monitoring of the immune response of vaccinated patients.

Efforts have been devoted to set up assays that accurately monitor CD4+ T cell responses to cancer vaccines. For patients vaccinated with a protein, we have validated a quantitative approach to isolate anti-vaccine T cells directed at all possible HLA-peptide combinations that could be targeted by the response. For patients vaccinated with a peptide, we have validated the use of the first HLA-DP4 tetramer, which was folded with a MAGE-3 peptide. By screening blood cells of vaccinated patients with this tetramer, we found that injections of the MAGE-3.DP4 peptide resulted in the activation and proliferation of specific T cells with various cytokine profiles, including IL-10-producing T cells and regulatory T cells.

The group is currently involved in the study of functional defects of T cells. We have observed that human CTL clones lose their specific cytolytic activity and cytokine production under certain stimulation conditions. These inactive CTL simultaneously lose their labeling by an HLA-peptide tetramer, even though the amount of TCR-CD3 at their surface is not reduced. These results suggest the existence of a new type of functional defect of CTL.

Selected publications


  1. van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 1991;254:1643-7
  2. van der Bruggen P, Zhang Y, Chaux P, Stroobant V, Panichelli C, Schultz ES, Chapiro J, Van den Eynde BJ, Brasseur F, Boon T. Tumor-specific shared antigenic peptides recognized by human T cells. Immunol Rev 2002;188:51-64.
  3. Sun Z, Lethé B, Zhang Y, Russo V, Colau D, Stroobant V, Boon T, van der Bruggen P. A new LAGE-1 peptide recognized by cytolytic T lymphocytes on HLA-A68 tumors. Cancer Immunol Immunother 2006;55:644-52.
  4. Ottaviani S, Colau D, van der Bruggen P. A new MAGE-4 antigenic peptide recognized by cytolytic T lymphocytes on HLA–A24 carcinoma cells. Cancer Immunol Immunother 2006;55:867-72.
  5. Chaux P, Vantomme V, Stroobant V, Thielemans K, Corthals J, Luiten R, Eggermont AM, Boon T, van der Bruggen P. Identification of MAGE-3 epitopes presented by HLA-DR molecules to CD4(+) T lymphocytes. J Exp Med 1999;189:767-78.
  6. van de Corput L, Chaux P, van der Meijden ED, De Plaen E, Falkenburg JHF, van der Bruggen P. A novel approach to identify antigens recognized by CD4 T cells using complement-opsonized bacteria expressing a cDNA library. Leukemia 2005;19:279-85.
  7. Zhang Y, Renkvist N, Sun Z, Schuler-Thurner B, Glaichenhaus N, Schuler G, Boon T, van der Bruggen P, Colau D. A polyclonal anti-vaccine CD4 T cell response detected with HLA-DP4 multimers in a melanoma patient vaccinated with MAGE-3.DP4-peptide-pulsed dendritic cells. Eur J Immunol 2005;35:1066-75.
  8. Zhang Y, Sun Z, Nicolay H, Meyer RG, Renkvist N, Stroobant V, Corthals J, Carrasco J, Eggermont AM, Marchand M, Thielemans K, Wolfel T, Boon T, van der Bruggen P. Monitoring of anti-vaccine CD4 T cell frequencies in melanoma patients vaccinated with a MAGE-3 protein. J Immunol 2005;174:2404-11.
  9. Demotte N, Colau D, Ottaviani S, Godelaine D, Van Pel A, Boon T, van der Bruggen P. A reversible functional defect of CD8+ T lymphocytes involving loss of tetramer labeling. Eur J Immunol 2002;32:1688-97.
  10. Graham SP, Pelle R, Honda Y, Mwangi DM, Tonukari NJ, Yamage M, Glew EJ, de Villiers EP, Shah T, Bishop R, Abuya E, Awino E, Gachanja J, Luyai AE, Mbwika F, Muthiani AM, Ndegwa DM, Njahira M, Nyanjui JK, Onono FO, Osaso J, Saya RM, Wildmann C, Fraser CM, Maudlin I, Gardner MJ, Morzaria SP, Loosmore S, Gilbert SC, Audonnet JC, van der Bruggen P, Nene V, Taracha EL. Theileria parva candidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes. Proc Natl Acad Sci U S A 2006;103:3286-91.

Publications