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Generation of specific anti-melanoma reactivity by stimulation of human tumor-infiltrating lymphocytes with MAGE-1 synthetic peptide

  • Original Articles
  • Melanoma, MAGE-1, Tumor-Infiltrating Lymphocytes, Immunotherapy, Peptide
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

The MAGE-1 gene encodes a tumor-specific antigen, MZ2-E, which is recognized by cloned, specific cytolytic T cells (CTL) derived from the peripheral blood of a patient with melanoma. We have produced a MAGE-1-specific CTL line derived from the tumor-infiltrating lymphocytes (TIL) of a melanoma patient by weekly restimulation with autologous EBV-B cells pulsed with the synthetic HLA-A1-restricted MAGE-1 epitope nonapeptide EADPTGHSY. The 1277. A TIL line grew in long-term culture in low-dose interleukin-2 (IL-2) and IL-4, and exhibited antigen-specific, MHC-class-I-restricted lysis of HLA-A1-bearing MAGE-1+ cell lines. Cytolysis of target cells pulsed with the synthetic MAGE-1 decapeptide KEADPTGHSY was superior to that of cells pulsed with the immunodominant nonapeptide. Single amino-acid or even side-chain substitutions in the immunodominant nonamer abrogated cytolysis. 1277. A TIL specifically secreted tumor necrosis factor α after co-incubation with HLA-A1-expressing MAGE-1+ cell lines or fresh tumor. These data suggest that tumor-antigen-specific, MHC-restricted CTL may be grown from TIL in the presence of synthetic epitope peptides and expanded for adoptive immunotherapy in melanoma patients.

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References

  1. Anichini A, Fossati G, Parmiani G (1987) Clonal analysis of the cytolytic T-cell response to human tumors. Immunol Today 385

  2. Anichini M, Maccalli C, Mortarini R, Salvi S, Mazzocchi A, Squarcina P, Herlyn M, Parmiani G (1993) Melanoma cells and normal melanocytes share antigens recognized by HLA-A2-restricted cytotoxic T cell clones from melanoma patients. J Exp Med 177: 989

    PubMed  Google Scholar 

  3. Barth RJ, Mulé JJ, Spiess PJ, Rosenberg SA (1991) Interferon gamma and tumor necrosis factor have a role in tumor regressions mediated by murine CD8+ tumor-infiltrating lymphocytes. J Exp Med 173: 647

    PubMed  Google Scholar 

  4. Boon T (1992) Toward a genetic analysis of tumor rejection antigens. In: Advances in cancer research. Academic Press, New York, p 177

    Google Scholar 

  5. Boon T (1993) Tumor antigens recognized by cytolytic T lymphocytes: present perspectives for specific immunotherapy. Int J Cancer 54: 177

    PubMed  Google Scholar 

  6. Brasseur F, Marchand M, Vanwijck R, Hérin M, Lethé B, Chomez P, Boon T (1992) Human gene MAGE-1, which codes for a tumor-rejection antigen, is expressed by some breast tumors. Int J Cancer 52: 839

    PubMed  Google Scholar 

  7. Brichard V, Van Pel A, Wölfel T, Wölfel C, De Plaen E, Lethé B, Coulie PG, Boon T (1993) The tyrosinase gene codes for an antigen recognized by autologous cytotoxic T lymphocytes on HLA-A2 melanoma. J Exp Med 178: 489

    PubMed  Google Scholar 

  8. Bystryn J-C (1993) Tumor vaccines. Cancer Metastasis Rev 9: 81

    Google Scholar 

  9. Carreno BM, Turner RV, Biddison WE, Coligan JE (1992) Overlapping epitopes that are recognized by CD8+ HLA class I-restricted and CD4+ class II-restricted cytotoxic T lymphocytes are contained within and influenza nucleoprotein peptide. J Immunol 148: 894

    PubMed  Google Scholar 

  10. Cheever MA, Thompson DB, Klarnet JP, Greenberg PD (1986) Antigen-driven long-term cultured T cells proliferate in vivo, distribute widely, mediate specific tumor therapy and persist long-term as functional memory T cells. J Exp Med 163: 1100

    PubMed  Google Scholar 

  11. Chen BP, DeMars R, Sondel PM (1987) Presentation of soluble antigen to human T cells by products of multiple HLA-linked loci: analysis of antigen presentation by a panel of cloned, autologous, HLA-mutant epstein-barr virus-transformed lymphoblastoid cell lines. Hum Immunol 18: 75

    PubMed  Google Scholar 

  12. Chestnut RW, Grey HM (1986) Antigen presentation by B cells and its significance in T-B interactions. Adv Immunol 39: 51

    PubMed  Google Scholar 

  13. Coulie PG, Somville M, Lehmann F, Hainaut P, Brasseur F, Devos R, Boon T (1992) Precursor frequency analysis of human cytolytic T lymphocytes directed against autologous melanoma cells. Int J Cancer 50: 289

    PubMed  Google Scholar 

  14. Darrow TL, Slingluff CL Jr, Seigler HF (1989) The role of HLA class I antigens in recognition of melanoma cells by tumor-specific cytotoxic T lymphocytes. J Immunol 142: 3329

    PubMed  Google Scholar 

  15. De Plaen E, Lurquin C, Van Pel A, Mariame B, Szikora J, Wolfel T, Sibille C, Chomez P, Boon T (1988) Immunogenic (tum−) variants of mouse tumor P815: cloning of the gene of tumantigen P91A and identification of the tum− mutation. Proc Natl Acad Sci USA 85: 2274

    PubMed  Google Scholar 

  16. Elliott BE, Carlow DA, Rodricks A-M, Wade A (1989) Perspectives on the role of MHC antigens in normal and malignant cell development. Adv Cancer Res 53: 181

    PubMed  Google Scholar 

  17. Elliott T, Townsend A, Cerundolo V (1990) Naturally processed peptides. Nature 348: 195

    PubMed  Google Scholar 

  18. Feltkamp MCW, Smits HL, Vierboom MPM, Minnaar RP, Jongh BM de, Drijhout JW, Shegget J ter, Melief CJ, MKast WM (1993) Vaccination with cytotoxic T lymphocyte epitope-containing peptide protects against a tumor induced by human papillomavirus type 16-transformed cells. Eur J Immunol 23: 2242

    PubMed  Google Scholar 

  19. Hellström KE, Hellström I (1991) Principles of tumor immunity: tumor antigens. In: DeVita VT, Hellman S, Rosenberg SA (eds) Biologic therapy of cancer. Lippincott, Philadelphia, p 35

    Google Scholar 

  20. Hom SS, Schwartzentruber DJ, Rosenberg SA, Topalian SL (1993) Specific release of cytokines by lymphocytes infiltrating human melanomas in response to shared melanoma antigens. J Immunol Methods 13: 18

    Google Scholar 

  21. Hu S-L, Hellström I, Hellström KE (1992) Recent advances in antitumor vaccines. In: Ellis RW (ed). Vaccines: new approaches to immunological problems. Butterworth-Heinemann, Boston, p 327

    Google Scholar 

  22. Inaba K, Metlay JP, Crowley MT, Steinman RM (1990) Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J Exp Med 172: 631

    PubMed  Google Scholar 

  23. Issekutz T, Chu E, Geha RS (1982) Antigen presentation by human B cells: T cell proliferation induced by Epstein Barr virus B lymphoblastoid cells. J Immunol 129: 1446

    PubMed  Google Scholar 

  24. Kahn M, Sugawara H, McGowan P, Okuno K, Nagoya S, Hellström KE, Hellström I, Greenberg P (1991) CD4+ cell clones specific for the human p97 melanoma-associated antigen can eradicate pulmonary metastases from a murine tumor expressing the p97 antigen. J Immunol 146: 3235

    PubMed  Google Scholar 

  25. Kawakami Y, Zakut R, Topalian SL, Stötter H, Rosenberg SA (1992) Shared human melanoma antigens: recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. J Immunol 148: 638

    PubMed  Google Scholar 

  26. Klarnet JP, Matis LA, Kern DE, Mizuno MT, Peace DJ, Thompson JA, Greenberg PD, Cheever MA (1987) Antigen-driven T cell clones can proliferate in vivo, eradicate disseminated lenkemia and provide specific immunologic memory. J Immunol 138: 4012

    PubMed  Google Scholar 

  27. Klein G, Sjögren HO, Klein E, Hellström KE (1960) Demonstration of resistance against methylcholanthrene-induced sarcomas in the primary autochthonous host. Cancer Res 20: 1561

    PubMed  Google Scholar 

  28. Lurquin C, Van Pel A, Mariame B, De Plaen E, Szikora J, Janssens C, Reddehase M, Lejeune J, Boon T (1989) Structure of the gene coding for tum− transplantation antigen P91A. Cell 58: 293

    PubMed  Google Scholar 

  29. Quentmeier H, Klaucke J, Mühlradt PF, Drexler HG (1992) Role of IL-6, IL-2, and IL-4 in the in vitro induction of cytotoxic T cells. J Immunol 149: 3316

    PubMed  Google Scholar 

  30. Restifo NP (1992) Antigen processing and presentation: an update. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds) Biologic therapy of cancer. Lippincott, Philadelphia, p 1

    Google Scholar 

  31. Restifo NP, Spiess PJ, Karp SE, Mulé JJ, Rosenberg SA (1992) A nonimmunogenic sarcoma transduced with the cDNA for interferon gamma elicits CD8+ T cells against the wild-type tumor: correlation with antigen presentation capability. J Exp Med 175: 1423

    PubMed  Google Scholar 

  32. Restifo NP, Esquivel F, Kawakami Y, Yewdell JM, Mulé JJ, Rosenberg SA, Bennick JR (1993) Identification of human cancers deficient in antigen processing. J Exp Med 177: 265

    PubMed  Google Scholar 

  33. Riddell SR, Watanabe KS, Goodrich JM, Li CR, Agha ME, Greenberg PD (1992) Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science 257: 238

    PubMed  Google Scholar 

  34. Rosenberg SA, Spiess PS, Lafreniere R (1986) A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233: 1318

    PubMed  Google Scholar 

  35. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, White DE (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokineactivated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316: 889

    PubMed  Google Scholar 

  36. Rosenberg SA, Packard B, Aebersold P, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA, Simpson, C, Carter C, Bock S, Schwartzentruber D, Wei JP, White DE (1988) Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. N Engl J Med 319: 1676

    PubMed  Google Scholar 

  37. Schild H, Norda M, Deres K, Falk K, Rötzschke O, Wiesmüller K-H, Jung G, Rammensee H-G (1991) Fine specificity of cytotoxic T lymphocytes primed in vivo either with virus or synthetic lipopeptide vaccine or primed in vitro with peptide. J Exp Med 174: 1665

    PubMed  Google Scholar 

  38. Schreiber H, Ward PL, Rowley DA, Stauss HJ (1988) Unique tumor-specific antigens. Adv Cancer Res 6: 465

    Google Scholar 

  39. Schwartzentruber DJ, Topalian SL, Mancini M, Rosenberg SA (1991) Specific release of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and IFN-gamma by human tumor infiltrating lymphocytes after autologous tumor stimulation. J Immunol 146: 3674

    PubMed  Google Scholar 

  40. Sibille C, Chomez P, Wildmann C, Van Pel A, De Plaen E, Maryanski JL, Bergeyck V de, Boon T (1990) Structure of the gene of tum− transplantation antigen P198: a point mutation generates a new antigenic peptide. J Exp Med 173: 35

    Google Scholar 

  41. Skipper J, Stauss HJ (1993) Identification of two cytotoxic T lymphocytes-recognized epitopes in the ras protein. J Exp Med 177: 1493

    PubMed  Google Scholar 

  42. Sporn JR, Ergin MT, Robbins GR, Cable RG, Silver H, Mukherji B (1993) Adoptive immunotherapy with peripheral blood lymphocytes cocultured in vitro with autologous tumor cells and interleukin-2. Cancer Immunol Immunother 37: 175

    PubMed  Google Scholar 

  43. Tanaka K, Yoshioka T, Bieberich C, Jay G (1988) Role of the major histocompatability complex class I antigens in tumor growth and metastasis. Annu Rev Immunol 6: 359

    PubMed  Google Scholar 

  44. Topalian SL, Muul LM, Solomon D, Rosenberg SA (1987) Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. J Immunol Methods 102: 127

    PubMed  Google Scholar 

  45. Topalian SL, Solomon D, Rosenberg SA (1989) Tumor-specific cytolysis by lymphocytes infiltrating human melanomas. J Immunol 142: 3714

    PubMed  Google Scholar 

  46. Townsend A, Bodmer H (1989) Antigen recognition by class I-restricted T lymphocytes. Annu Rev Immunol 7: 601

    PubMed  Google Scholar 

  47. Townsend ARM, Rothbard J, Gotch FM, Bahadur G, Wraith D, McMichael AJ (1986) The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44: 959

    PubMed  Google Scholar 

  48. Traversari C, Van der Bruggen P, Luescher IF, Lurquin C, Chomez P, Van Pel A, De Plain E, Amar-Costesec A (1992) A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by CTL directed against tumor antigen MZ2-E. J Exp Med 176: 1453

    PubMed  Google Scholar 

  49. 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

    PubMed  Google Scholar 

  50. Utz U, Koenig S, Coligan JE, Biddison WE (1992) Presentation of three different viral peptides, HTLV-1 TAX, HCMV gB, and influenza virus M1, is determined by common structural features of the HLA-A2.1 molecule. J Immunol 149: 214

    PubMed  Google Scholar 

  51. Van den Eynde B, Lethé B, Van Pel A, De Plaen E, Boon T (1991) The gene coding for a major tumor rejection antigen to tumor P815 is identical to the normal gene of syngeneic DBA/2 mice. J Exp Med 173: 1373

    PubMed  Google Scholar 

  52. Van der Bruggen P, Traversari C, Chomez P, Lurquin C, DePlaen E, Van den Eynde B, Kunth A, Boon T (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on human melanoma. Science 254: 1643

    PubMed  Google Scholar 

  53. Weber J, Salgaller M, Samid D, Johnson B, Herlyn M, Lassam N, Treisman J, Rosenberg SA (1994) Expression of the MAGE-1 tumor antigen is upregulated by the demethylating agent 5 aza 2′ deoxycytidine. Cancer Res (in press)

  54. Yanuck M, Carbone DP, Pendleton CD, Tsukui T, Winter SF, Minna JD, Berzofsky JA (1993) A mutant p53 tumor suppressor protein is a target for peptide-induced CD8+ cytotoxic T-cells. Cancer Res 53: 3257

    PubMed  Google Scholar 

  55. Yasutomi Y, Koenig S, Haun SS, Stover CK, Jackson RK, Conard P, Conley AJ, Emini EA, Fuerst TR, Letvin NL (1993) Immunization with recombinant BCG-SIV elicits SIV-specific cytotoxic T lymphocytes in rhesus monkeys. J Immunol 150: 3101

    PubMed  Google Scholar 

  56. Zakut R, Topalian SL, Kawakami Y, Mancini M, Eliyahu S, Rosenberg SA (1993) Differential expression of MAGE-1,-2,-3 messenger RNA in transformed and normal human cell lines. Cancer Res 53: 54

    Google Scholar 

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Authors and Affiliations

  1. Surgery Branch, National Cancer Institute, National Institute of Health, Building 10, Room 2B08, 20892, Bethesda, Maryland, USA

    Michael L. Salgaller, Jeffrey S. Weber, John R. Yannelli & Steven A. Rosenberg

  2. Medimmune Inc., 20877, Gaithersburg, Maryland, USA

    Scott Koenig

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  1. Michael L. Salgaller
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  2. Jeffrey S. Weber
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  4. John R. Yannelli
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  5. Steven A. Rosenberg
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Salgaller, M.L., Weber, J.S., Koenig, S. et al. Generation of specific anti-melanoma reactivity by stimulation of human tumor-infiltrating lymphocytes with MAGE-1 synthetic peptide. Cancer Immunol Immunother 39, 105–116 (1994). https://doi.org/10.1007/BF01525316

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  • DOI: https://doi.org/10.1007/BF01525316

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