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Cancer Immunology, Immunotherapy

, Volume 55, Issue 6, pp 644–652 | Cite as

A new LAGE-1 peptide recognized by cytolytic T lymphocytes on HLA-A68 tumors

  • Zhaojun Sun
  • Bernard Lethé
  • Yi Zhang
  • Vincenzo Russo
  • Didier Colau
  • Vincent Stroobant
  • Thierry Boon
  • Pierre van der BruggenEmail author
Original Article

Abstract

Antigens encoded by genes of the LAGE family, including LAGE-1 and NY-ESO-1, are of interest for cancer immunotherapy because they are tumor-specific and shared by tumors of different histological types. Several clinical trials are in progress with NY-ESO-1 peptides, protein, recombinant poxviruses, and dendritic cells pulsed with peptides. In this study, CD8 T lymphocytes from an individual without cancer were stimulated with dendritic cells infected with a recombinant avian poxvirus encoding a complete LAGE-1 protein. A CTL clone was isolated that recognized a new LAGE-1 peptide, ELVRRILSR, which corresponds to position 103–111 of the protein sequence. It is presented by HLA-A6801 molecules. When tumor cells expressing LAGE-1 were transfected with HLA-A68, they were lysed by the CTL clone, indicating that the peptide is processed in tumor cells. These results indicate that the LAGE-1.A68 peptide can be used for antitumoral vaccination. We observed also that specific T cells could be detected in a blood sample with a high sensitivity by using an A68/LAGE-1 fluorescent multimer.

Keywords

HLA-A68 LAGE-1 Peptide Poxvirus SNP Tumor 

Notes

Acknowledgements

We thank Dr. Pierre Coulie for the critical reading and Mrs Nathalie Krack for the editorial assistance. This work was supported by the Belgian Programme on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister’s Office, Science Policy Programming, and by a grant from the Fédération Belge contre le Cancer (Belgium).

References

  1. 1.
    Aarnoudse CA, van den Doel PB, Heemskerk B, Schrier PI (1999) Interleukin-2-induced, melanoma-specific T cells recognize camel, an unexpected translation product of LAGE-1. Int J Cancer 82:442–448PubMedCrossRefGoogle Scholar
  2. 2.
    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 274:94–96PubMedCrossRefGoogle Scholar
  3. 3.
    Baurain J-F, Colau D, van Baren N, Landry C, Martelange V, Vikkula M, Boon T, Coulie PG (2000) High frequency of autologous anti-melanoma CTLs directed against an antigen generated by a point mutation in a new helicase gene. J Immunol 164:6057–6066PubMedGoogle Scholar
  4. 4.
    Benlalam H, Linard B, Guilloux Y, Moreau-Aubry A, Derré L, Diez E, Dreno B, Jotereau F, Labarrière N (2003) Identification of five new HLA-B*3501-restricted epitopes derived from common melanoma-associated antigens, spontaneously recognized by tumor-infiltrating lymphocytes. J Immunol 171:6283–6289PubMedGoogle Scholar
  5. 5.
    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 2:167–175PubMedCrossRefGoogle Scholar
  6. 6.
    Chen J-L, Dunbar PR, Gileadi U, Jäger E, Gnjatic S, Nagata Y, Stockert E, Panicali DL, Chen Y-T, Knuth A, Old LJ, Cerundolo V (2000) Identification of NY-ESO-1 peptide analogues capable of improved stimulation of tumor-reactive CTL. J Immunol 165:948–955PubMedGoogle Scholar
  7. 7.
    Chen Q, Jackson H, Parente P, Luke T, Rizkalla M, Tai TY, Zhu HC, Mifsud NA, Dimopoulos N, Masterman KA, Hopkins W, Goldie H, Maraskovsky E, Green S, Miloradovic L, McCluskey J, Old LJ, Davis ID, Cebon J, Chen W (2004) Immunodominant CD4+ responses identified in a patient vaccinated with full-length NY-ESO-1 formulated with ISCOMATRIX adjuvant. Proc Natl Acad Sci USA 101:9363–9368PubMedCrossRefGoogle Scholar
  8. 8.
    Chen Q, Jackson H, Shackleton M, Parente P, Hopkins W, Sturrock S, MacGregor D, Maraskovsky E, Tai TY, Dimopoulos N, Masterman KA, Luke T, Davis ID, Chen W, Cebon J (2005) Characterization of antigen-specific CD8+ T lymphocyte responses in skin and peripheral blood following intradermal peptide vaccination. Cancer Immun 5:5PubMedGoogle Scholar
  9. 9.
    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 94:1914–1918PubMedCrossRefGoogle Scholar
  10. 10.
    Davis ID, Chen W, Jackson H, Parente P, Shackleton M, Hopkins W, Chen Q, Dimopoulos N, Luke T, Murphy R, Scott AM, Maraskovsky E, McArthur G, MacGregor D, Sturrock S, Tai TY, Green S, Cuthbertson A, Maher D, Miloradovic L, Mitchell SV, Ritter G, Jungbluth AA, Chen YT, Gnjatic S, Hoffman EW, Old LJ, Cebon JS (2004) Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4+ and CD8+ T cell responses in humans. Proc Natl Acad Sci USA 101:10697–10702PubMedCrossRefGoogle Scholar
  11. 11.
    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 59:3157–3165PubMedGoogle Scholar
  12. 12.
    De Plaen E, Arden K, Traversari C, Gaforio JJ, Szikora J-P, De Smet C, Brasseur F, van der Bruggen P, Lethé B, Lurquin C, Brasseur R, Chomez P, De Backer O, Cavenee W, Boon T (1994) Structure, chromosomal localization and expression of twelve genes of the MAGE family. Immunogenetics 40:360–369PubMedCrossRefGoogle Scholar
  13. 13.
    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 29:3329–3337PubMedCrossRefGoogle Scholar
  14. 14.
    Espevik T, Nissen-Meyer J (1986) A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes. J Immunol Methods 95:99–105PubMedCrossRefGoogle Scholar
  15. 15.
    Gnjatic S, Nagata Y, Jäger E, Stockert E, Shankara S, Roberts BL, Mazzara GP, Lee SY, Dunbar PR, Dupont B, Cerundolo V, Ritter G, Chen YT, Knuth A, Old LJ (2000) Strategy for monitoring T cell responses to NY-ESO-1 in patients with any HLA class I allele. Proc Natl Acad Sci USA 97:10917–10922PubMedCrossRefGoogle Scholar
  16. 16.
    Guo H-C, Jardetzky TS, Garrett TPJ, Lane WS, Strominger JL, Wiley DC (1992) Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle. Nature 360:364–366PubMedCrossRefGoogle Scholar
  17. 17.
    Haas GG Jr, D’Cruz OJ, De Bault LE (1988) Distribution of human leukocyte antigen-ABC and -D/DR antigens in the unfixed human testis. Am J Reprod Immunol Microbiol 18:47–51PubMedGoogle Scholar
  18. 18.
    Hansen MB, Nielsen SE, Berg K (1989) Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods 119:203–210PubMedCrossRefGoogle Scholar
  19. 19.
    Herman J, van der Bruggen P, Luescher I, Mandruzzato S, Romero P, Thonnard J, Fleischhauer K, Boon T, Coulie PG (1996) A peptide encoded by the human gene MAGE-3 and presented by HLA-B44 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3. Immunogenetics 43:377–383PubMedCrossRefGoogle Scholar
  20. 20.
    Herman J, Jongeneel V, Kuznetsov D, Coulie PG (1999) Differences in the recognition by CTL of peptides presented by the HLA-B*4402 and the HLA-B*4403 molecules which differ by a single amino acid. Tissue Antigens 53:111–121PubMedCrossRefGoogle Scholar
  21. 21.
    Jäger E, Chen Y-T, Drijfhout JW, Karbach J, Ringhoffer M, Jäger D, Arand M, Wada H, Noguchi Y, Stockert E, Old LJ, Knuth A (1998) Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes. J Exp Med 187:265–270PubMedCrossRefGoogle Scholar
  22. 22.
    Jäger E, Karbach J, Gnjatic S, Jäger D, Maeurer M, Atmaca A, Arand M, Skipper J, Stockert E, Chen Y-T, Old LJ, Knuth A (2002) Identification of a naturally processed NY-ESO-1 peptide recognized by CD8+ T cells in the context of HLA-B51. Cancer Immun [serial online] 2:12Google Scholar
  23. 23.
    Khong HT, Yang JC, Topalian SL, Sherry RM, Mavroukakis SA, White DE, Rosenberg SA (2004) Immunization of HLA-A*0201 and/or HLA-DPb1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen. J Immunother 27:472–477PubMedCrossRefGoogle Scholar
  24. 24.
    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 25:340–347PubMedCrossRefGoogle Scholar
  25. 25.
    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 76:903–908PubMedCrossRefGoogle Scholar
  26. 26.
    Marsh SGE, Parham P, Barber LD (eds) (2000) The HLA facts book. Academic, LondonGoogle Scholar
  27. 27.
    Rimoldi D, Rubio-Godoy V, Dutoit V, Liénard D, Salvi S, Guillaume P, Speiser D, Stockert E, Spagnoli G, Servis C, Cerottini J-C, Lejeune F, Romero P, Valmori D (2000) Efficient simultaneous presentation of NY-ESO-1/LAGE-1 primary and nonprimary open reading frame-derived CTL epitopes in melanoma. J Immunol 165:7253–7261PubMedGoogle Scholar
  28. 28.
    Romani N, Gruner S, Brang D, Kämpgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch PO, Steinman RM, Schuler G (1994) Proliferating dendritic cell progenitors in human blood. J Exp Med 180:83–93PubMedCrossRefGoogle Scholar
  29. 29.
    Sallusto F, Lanzavecchia A (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor a. J Exp Med 179:1109–1118PubMedCrossRefGoogle Scholar
  30. 30.
    Slager EH, van der Minne CE, Goudsmit J, van Oers JMM, Kostense S, Havenga MJE, Osanto S, Griffioen M (2004) Induction of CAMEL/NY-ESO-ORF2-specific CD8+ T cells upon stimulation with dendritic cells infected with a modified Ad5 vector expressing a chimeric Ad5/35 fiber. Cancer Gene Ther 11:227–236PubMedCrossRefGoogle Scholar
  31. 31.
    Traversari C, van der Bruggen P, Van den Eynde B, Hainaut P, Lemoine C, Ohta N, Old L, Boon T (1992) Transfection and expression of a gene coding for a human melanoma antigen recognized by autologous cytolytic T lymphocytes. Immunogenetics 35:145–152PubMedCrossRefGoogle Scholar
  32. 32.
    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 254:1643–1647PubMedCrossRefGoogle Scholar
  33. 33.
    Wang R-F, Johnston SL, Zeng G, Topalian SL, Schwartzentruber DJ, Rosenberg SA (1998) A breast and melanoma-shared tumor antigen: T cell responses to antigenic peptides translated from different open reading frames. J Immunol 161:3596–3606Google Scholar
  34. 34.
    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 60:365–371PubMedCrossRefGoogle Scholar
  35. 35.
    Zhang Y, Sun Z, Nicolay H, Meyer RG, Renkvist N, Stroobant V, Corthals J, Carrasco J, Eggermont AMM, Marchand M, Thielemans K, Wölfel T, Boon T, van der Bruggen P (2005) Monitoring of anti-vaccine CD4 T cell frequencies in melanoma patients vaccinated with a MAGE-3 protein. J Immunol 174:2404–2411PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Zhaojun Sun
    • 1
  • Bernard Lethé
    • 1
  • Yi Zhang
    • 1
    • 2
  • Vincenzo Russo
    • 3
  • Didier Colau
    • 1
  • Vincent Stroobant
    • 1
  • Thierry Boon
    • 1
  • Pierre van der Bruggen
    • 1
    Email author
  1. 1.Ludwig Institute for Cancer Research Institute of Cellular Pathology, Cellular Genetics UnitUniversité de LouvainBrusselsBelgium
  2. 2.Department of PathologyUniversity of ChicagoChicagoUSA
  3. 3.Cancer Immunotherapy and Gene Therapy ProgramScientific Institute H. San RaffaeleMilanoItaly

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