Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  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 82:442–448

    Article  PubMed  CAS  Google Scholar 

  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 274:94–96

    Article  PubMed  CAS  Google Scholar 

  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 164:6057–6066

    PubMed  CAS  Google Scholar 

  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 171:6283–6289

    PubMed  CAS  Google Scholar 

  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 2:167–175

    Article  PubMed  Google Scholar 

  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 165:948–955

    PubMed  CAS  Google Scholar 

  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 101:9363–9368

    Article  PubMed  CAS  Google Scholar 

  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 5:5

    PubMed  Google Scholar 

  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 94:1914–1918

    Article  PubMed  CAS  Google Scholar 

  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 101:10697–10702

    Article  PubMed  CAS  Google Scholar 

  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 59:3157–3165

    PubMed  CAS  Google Scholar 

  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 40:360–369

    Article  PubMed  CAS  Google Scholar 

  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 29:3329–3337

    Article  PubMed  CAS  Google Scholar 

  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 95:99–105

    Article  PubMed  CAS  Google Scholar 

  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 97:10917–10922

    Article  PubMed  CAS  Google Scholar 

  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 360:364–366

    Article  PubMed  CAS  Google Scholar 

  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 18:47–51

    PubMed  Google Scholar 

  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 119:203–210

    Article  PubMed  CAS  Google Scholar 

  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 43:377–383

    Article  PubMed  CAS  Google Scholar 

  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 53:111–121

    Article  PubMed  CAS  Google Scholar 

  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 187:265–270

    Article  PubMed  Google Scholar 

  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] 2:12

    Google Scholar 

  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 27:472–477

    Article  PubMed  CAS  Google Scholar 

  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 25:340–347

    Article  PubMed  CAS  Google Scholar 

  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 76:903–908

    Article  PubMed  Google Scholar 

  26. Marsh SGE, Parham P, Barber LD (eds) (2000) The HLA facts book. Academic, London

    Google Scholar 

  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 165:7253–7261

    PubMed  CAS  Google Scholar 

  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 180:83–93

    Article  PubMed  CAS  Google Scholar 

  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 179:1109–1118

    Article  PubMed  CAS  Google Scholar 

  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 11:227–236

    Article  PubMed  CAS  Google Scholar 

  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 35:145–152

    Article  PubMed  CAS  Google Scholar 

  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 254:1643–1647

    Article  PubMed  Google Scholar 

  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 161:3596–3606

    CAS  Google Scholar 

  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 60:365–371

    Article  PubMed  CAS  Google Scholar 

  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 174:2404–2411

    PubMed  CAS  Google Scholar 

Download references

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).

Author information

Author notes

  1. Vincenzo Russo

    Present address: Cancer Immunotherapy and Gene Therapy Program, Scientific Institute H. San Raffaele, 58 via Olgettina, I-20132, Milano, Italy

Authors and Affiliations

  1. Ludwig Institute for Cancer Research Institute of Cellular Pathology, Cellular Genetics Unit, Université de Louvain, 74 avenue Hippocrate, UCL 7459, 1200, Brussels, Belgium

    Zhaojun Sun, Bernard Lethé, Yi Zhang, Didier Colau, Vincent Stroobant, Thierry Boon & Pierre van der Bruggen

  2. Department of Pathology, University of Chicago, 5841 S. Maryland Ave., MC 3008, Chicago, IL, 60637, USA

    Yi Zhang

Authors
  1. Zhaojun Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bernard Lethé
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vincenzo Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Didier Colau
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vincent Stroobant
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Thierry Boon
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pierre van der Bruggen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pierre van der Bruggen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sun, Z., Lethé, B., Zhang, Y. et al. A new LAGE-1 peptide recognized by cytolytic T lymphocytes on HLA-A68 tumors. Cancer Immunol Immunother 55, 644–652 (2006). https://doi.org/10.1007/s00262-005-0066-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-005-0066-x

Keywords

Search

Navigation