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A new MAGE-4 antigenic peptide recognized by cytolytic T lymphocytes on HLA-A24 carcinoma cells.

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Ottaviani, Sabrina [UCL] Colau, Didier [UCL] van der Bruggen, Pierre [UCL]

"Cancer-germline" genes such as those of the MAGE family are expressed in many tumors and in male germline cells, but are silent in other normal tissues. They encode tumor specific antigens that are used in cancer immunotherapy trials. MAGE-4 antigens represent promising targets for cancer immunotherapy because gene MAGE-4 is expressed in more than 50% of carcinomas of the esophagus, lung, bladder, and head and neck. To identify new MAGE-4 antigenic peptides, we have folded HLA-A*2402 soluble molecules with candidate peptide NYKRCFPVI, which corresponds to amino acids 143 to151 of the MAGE-4 protein. A24/MAGE-4 multimers were used to isolate a cytolytic T cell clone that recognized the MAGE-4 peptide from the blood cells of a donor without cancer. This clone lysed specifically A24 carcinoma cells expressing MAGE-4. The antigenic peptide is processed more efficiently in tumor cells pre-treated with IFN-gamma. This MAGE-4 peptide could represent an interesting target for immunotherapy because it is presented by HLA-A24 molecules, which are widely expressed in different ethnic groups.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2006
Journal information "Cancer Immunology Immunotherapy" - Vol. 55, no. 7, p. 867-872 (2006)
Peer reviewed yes
Publisher Springer ((Germany) Heidelberg)
issn 0340-7004
e-issn 1432-0851
Publication status Publié
Affiliation UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique
MESH Subject Amino Acid Sequence ; Animals ; Antigens, Neoplasm - immunology ; COS Cells ; Carcinoma - immunology - pathology ; Cell Line, Transformed ; Cell Line, Tumor ; Cercopithecus aethiops ; Cytotoxicity, Immunologic ; Dendritic Cells - immunology ; HLA-A Antigens - immunology ; Herpesvirus 4, Human ; Humans ; Interferon-gamma - biosynthesis ; Molecular Sequence Data ; Neoplasm Proteins - immunology ; Peptide Fragments - immunology ; Protein Folding ; Recombinant Fusion Proteins - immunology ; T-Lymphocytes, Cytotoxic - immunology ; Transfection
Keywords Carcinoma ; CTL ; HLA-A24 ; MAGE-4 ; Peptide ; Tumor
Links
  1. Altman JD, Moss PAH, Goulder PJR, Barouch DH, McHeyzer-Williams MG, Bell JI, McMichael AJ, Davis MM (1996) Phenotypic analysis of antigen-specific T lymphocytes. Science 274:94–96
  2. Bettinotti MP, Panelli MC, Ruppe E, Mocellin S, Phan GQ, White DE, Marincola FM (2003) Clinical and immunological evaluation of patients with metastatic melanoma undergoing immunization with the HLA-Cw*0702-associated epitope MAGE-A12:170–178. Int J Cancer 105:210–216
  3. Boël P, Wildmann C, Sensi M-L, Brasseur R, Renauld J-C, Coulie P, Boon T, van der Bruggen P (1995) BAGE, a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity 2:167–175
  4. Boon T, Cerottini J-C, Van den Eynde B, van der Bruggen P, Van Pel A (1994) Tumor antigens recognized by T lymphocytes. Annu Rev Immunol 12:337–365
  5. Chaux P, Luiten R, Demotte N, Vantomme V, Stroobant V, Traversari C, Russo V, Schultz E, Cornelis GR, Boon T, van der Bruggen P (1999) Identification of five MAGE-A1 epitopes recognized by cytolytic T lymphocytes obtained by in vitro stimulation with dendritic cells transduced with MAGE-A1. J Immunol 163:2928–2936
  6. Chen Y-T, Scanlan MJ, Sahin U, Türeci Ö, Gure AO, Tsang S, Williamson B, Stockert E, Pfreundschuh M, Old LJ (1997) A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA 94:1914–1918
  7. De Backer O, Arden KC, Boretti M, Vantomme V, De Smet C, Czekay S, Viars CS, De Plaen E, Brasseur F, Chomez P, Van den Eynde B, Boon T, van der Bruggen P (1999) Characterization of the GAGE genes that are expressed in various human cancers and in normal testis. Cancer Res 59:3157–3165
  8. Duffour M-T, Chaux P, Lurquin C, Cornelis G, Boon T, van der Bruggen P (1999) A MAGE-A4 peptide presented by HLA-A2 is recognized by cytolytic T lymphocytes. Eur J Immunol 29:3329–3337
  9. Fujie T, Tahara K, Tanaka F, Mori M, Takesako K, Akiyoshi T (1999) A MAGE-1-encoded HLA–A24-binding synthetic peptide induces specific anti-tumor cytotoxic T lymphocytes. Int J Cancer 80:169–172
  10. Gure AO, Türeci Ö, Sahin U, Tsang S, Scanlan MJ, Jäger E, Knuth A, Pfreundschuh M, Old LJ, Chen Y-T (1997) SSX: a multigene family with several members transcribed in normal testis and human cancer. Int J Cancer 72:965–971
  11. HAAS GILBERT G., D'CRUZ OSMOND J., DE BAULT LAWRENCE E., Distribution of Human Leukocyte Antigen-ABC and -D/DR Antigens in the Unfixed Human Testis, 10.1111/j.1600-0897.1988.tb00234.x
  12. Hersey P, Menzies SW, Coventry B, Nguyen T, Farrelly M, Collins S, Hirst D, Johnson H (2005) Phase I/II study of immunotherapy with T-cell peptide epitopes in patients with stage IV melanoma. Cancer Immunol Immunother 54:208–218
  13. Ikeda H, Lethé B, Lehmann F, Van Baren N, Baurain J-F, De Smet C, Chambost H, Vitale M, Moretta A, Boon T, Coulie PG (1997) Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity 6:199–208
  14. Kobayashi T, Lonchay C, Colau D, Demotte N, Boon T, van der Bruggen P (2003) New MAGE-4 antigenic peptide recognized by cytolytic T lymphocytes on HLA-A1 tumor cells. Tissue Antigens 62:426–432
  15. Lehmann F, Marchand M, Hainaut P, Pouillart P, Sastre X, Ikeda H, Boon T, Coulie PG (1995) Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection. Eur J Immunol 25:340–347
  16. Lethé B, Lucas S, Michaux L, De Smet C, Godelaine D, Serrano A, De Plaen E, Boon T (1998) LAGE-1, a new gene with tumor specificity. Int J Cancer 76:903–908
  17. Luiten R, van der Bruggen P (2000) A MAGE-A1 peptide is recognized on HLA-B7 human tumors by cytolytic T lymphocytes. Tissue Antigens 55:149–152
  18. Marchand M, van Baren N, Weynants P, Brichard V, Dréno B, Tessier M-H, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Liénard D, Beauduin M, Dietrich P-Y, Russo V, Kerger J, Masucci G, Jäger E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van der Bruggen P, Boon T (1999) Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer 80:219–230
  19. Marsh SGE, Parham P, Barber LD (eds) (2000) The HLA FactsBook. Academic, London
  20. Ruault M, van der Bruggen P, Brun ME, Boyle S, Roizes G, De Sario A (2002) New BAGE (B melanoma antigen) genes mapping to the juxtacentromeric regions of human chromosomes 13 and 21 have a cancer/testis expression profile. Eur J Hum Genet 10:833–840
  21. Schultz ES, Zhang Y, Knowles R, Tine J, Traversari C, Boon T, van der Bruggen P (2001) A MAGE-3 peptide recognized on HLA-B35 and HLA-A1 by cytolytic T lymphocytes. Tissue Antigens 57:103–109
  22. Slingluff CL Jr, Petroni GR, Yamshchikov GV, Hibbitts S, Grosh WW, Chianese-Bullock KA, Bissonette EA, Barnd DL, Deacon DH, Patterson JW, Parekh J, Neese PY, Woodson EM, Wiernasz CJ, Merrill P (2004) Immunologic and clinical outcomes of vaccination with a multiepitope melanoma peptide vaccine plus low-dose interleukin-2 administered either concurrently or on a delayed schedule. J Clin Oncol 22:4474–4485
  23. Thurner B, Haendle I, Roder C, Dieckmann D, Keikavoussi P, Jonuleit H, Bender A, Maczek C, Schreiner D, von den Driesch P, Brocker EB, Steinman RM, Enk A, Kampgen E, Schuler G (1999) Vaccination with MAGE-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med 190:1669–1678
  24. Traversari C, van der Bruggen P, Luescher IF, Lurquin C, Chomez P, Van Pel A, De Plaen E, Amar-Costesec A, Boon T (1992) A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by cytolytic T lymphocytes directed against tumor antigen MZ2-E. J Exp Med 176:1453–1457
  25. Tureci O, Sahin U, Schobert I, Koslowski M, Scmitt H, Schild HJ, Stenner F, Seitz G, Rammensee H-G, Pfreundschuh M (1996) The SSX-2 gene, which is involved in the t(X;18) translocation of synovial sarcomas, codes for the human tumor antigen HOM-MEL-40. Cancer Res 56:4766–4772
  26. Van den Eynde B, Peeters O, De Backer O, Gaugler B, Lucas S, Boon T (1995) A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med 182:689–698
  27. Van den Eynde B, van der Bruggen P (2004) Peptide database of T-cell defined tumor antigens. Cancer Immunity http://www.cancerimmunity.org/peptidedatabase/Tcellepitopes.htm:
  28. van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254:1643–1647
  29. van der Bruggen P, Szikora J-P, Boël P, Wildmann C, Somville M, Sensi M, Boon T (1994) Autologous cytolytic T lymphocytes recognize a MAGE-1 nonapeptide on melanomas expressing HLA-Cw*1601. Eur J Immunol 24:2134–2140
  30. van der Bruggen P, Zhang Y, Chaux P, Stroobant V, Panichelli C, Schultz ES, Chapiro J, Van den Eynde BJ, Brasseur F, Boon T (2002) Tumor-specific shared antigenic peptides recognized by human T cells. Immunol Rev 188:51–64
  31. Zhang Y, Stroobant V, Russo V, Boon T, van der Bruggen P (2002) A MAGE-A4 peptide presented by HLA-B37 is recognized on human tumors by cytolytic T lymphocytes. Tissue Antigens 60:365–371
Bibliographic reference Ottaviani, Sabrina ; Colau, Didier ; van der Bruggen, Pierre. A new MAGE-4 antigenic peptide recognized by cytolytic T lymphocytes on HLA-A24 carcinoma cells.. In: Cancer Immunology Immunotherapy, Vol. 55, no. 7, p. 867-872 (2006)
Permanent URL http://hdl.handle.net/2078.1/29477