Skip to main content

Advertisement

SpringerLink
Log in

Immunotherapy of renal cell carcinoma

  • Symposium Paper
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Carcinomas of the kidney generally have a poor prognosis and respond minimally to classical radiotherapy or chemotherapy. Immunotherapy constitutes an interesting alternative to these established forms of treatment, and indeed, cytokine-based therapies have been used for many years, leading to favorable clinical responses in a small subset of patients. During the past few years, immunotherapeutical trials targeting renal cell tumor-associated antigens have also been reported, with diverse passive or active approaches using antibodies or aimed at activating tumor-directed T lymphocytes. The following review presents the results and the progress made in the field, including classical cytokine treatments, non-myeloablative stem cell transplantation and antigen specific-based trials, with special focus on T-cell studies. In consideration of the few specific molecular targets described so far for this tumor entity, current strategies which can lead to the identification of new relevant antigens will be discussed. Hopefully these will very soon contribute to an improvement in renal cell carcinoma specific immunotherapy and its evaluation.

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

Similar content being viewed by others

References

  1. Schrader AJ, Varga Z, Hegele A, Pfoertner S, Olbert P, Hofmann R (2006) Second-line strategies for metastatic renal cell carcinoma: classics and novel approaches. J Cancer Res Clin Oncol 132:137

    PubMed  CAS  Google Scholar 

  2. Rohrmann K, Staehler M, Haseke N, Bachmann A, Stief CG, Siebels M (2005) Immunotherapy in metastatic renal cell carcinoma. World J Urol 23:196

    PubMed  CAS  Google Scholar 

  3. Penn I (1995) Primary kidney tumors before and after renal transplantation. Transplantation 59:480

    PubMed  CAS  Google Scholar 

  4. Lokich J (1997) Spontaneous regression of metastatic renal cancer. Case report and literature review. Am J Clin Oncol 20:416

    PubMed  CAS  Google Scholar 

  5. Bukowski RM (1997) Natural history and therapy of metastatic renal cell carcinoma: the role of interleukin-2. Cancer 80:1198

    PubMed  CAS  Google Scholar 

  6. Fisher RI, Rosenberg SA, Fyfe G (2000) Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am 6(Suppl 1):S55–S57

    PubMed  Google Scholar 

  7. Minasian LM, Motzer RJ, Gluck L, Mazumdar M, Vlamis V, Krown SE (1993) Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up. J Clin Oncol 11:1368

    PubMed  CAS  Google Scholar 

  8. Motzer RJ, Murphy BA, Bacik J, Schwartz LH, Nanus DM, Mariani T, Loehrer P, Wilding G, Fairclough DL, Cella D, Mazumdar M (2000) Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma. J Clin Oncol 18:2972

    PubMed  CAS  Google Scholar 

  9. Negrier S, Escudier B, Lasset C, Douillard JY, Savary J, Chevreau C, Ravaud A, Mercatello A, Peny J, Mousseau M, Philip T, Tursz T (1998) Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Francais d’Immunotherapie. N Engl J Med 338:1272

    PubMed  CAS  Google Scholar 

  10. Bukowski RM (2000) Cytokine combinations: therapeutic use in patients with advanced renal cell carcinoma. Semin Oncol 27:204

    PubMed  CAS  Google Scholar 

  11. Ryan CW, Vogelzang NJ, Dumas MC, Kuzel T, Stadler WM (2000) Granulocyte-macrophage-colony stimulating factor in combination immunotherapy for patients with metastatic renal cell carcinoma: results of two phase II clinical trials. Cancer 88:1317

    PubMed  CAS  Google Scholar 

  12. Verra N, Jansen R, Groenewegen G, Mallo H, Kersten MJ, Bex A, Vyth-Dreese FA, Sein J, van de Kasteele W, Nooijen WJ, de Waal M, Horenblas S, de Gast GC (2003) Immunotherapy with concurrent subcutaneous GM-CSF, low-dose IL-2 and IFN-alpha in patients with progressive metastatic renal cell carcinoma. Br J Cancer 88:1346

    PubMed  CAS  Google Scholar 

  13. Escudier B, Farace F, Angevin E, Triebel F, Antoun S, Leclercq B, Brandely M, Aboudaram A, Nitenberg G, Hercend T (1993) Combination of interleukin-2 and gamma interferon in metastatic renal cell carcinoma. Eur J Cancer 29A:724

    PubMed  CAS  Google Scholar 

  14. Atzpodien J, Kirchner H, Jonas U, Bergmann L, Schott H, Heynemann H, Fornara P, Loening SA, Roigas J, Muller SC, Bodenstein H, Pomer S, Metzner B, Rebmann U, Oberneder R, Siebels M, Wandert T, Puchberger T, Reitz M (2004) Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a prospectively randomized trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). J Clin Oncol 22:1188

    PubMed  CAS  Google Scholar 

  15. Atzpodien J, Schmitt E, Gertenbach U, Fornara P, Heynemann H, Maskow A, Ecke M, Woltjen HH, Jentsch H, Wieland W, Wandert T, Reitz M (2005) Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). Br J Cancer 92:843

    PubMed  CAS  Google Scholar 

  16. Leppert JT, Lam JS, Belldegrun AS (2005) Predicting response to interleukin-2 therapy among patients with renal cell carcinoma. J Immunother 28:427

    PubMed  Google Scholar 

  17. Negrier S (2004) Better survival with interleukin-2-based regimens? Possibly only in highly selected patients. J Clin Oncol 22:1174

    PubMed  Google Scholar 

  18. Scheffold A, Huhn J, Hofer T (2005) Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL-)two to tango. Eur J Immunol 35:1336

    PubMed  CAS  Google Scholar 

  19. von Marschall Z, Scholz A, Cramer T, Schafer G, Schirner M, Oberg K, Wiedenmann B, Hocker M, Rosewicz S (2003) Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. J Natl Cancer Inst 95:437

    Article  Google Scholar 

  20. Donskov F, Bennedsgaard KM, von der Maase H, Marcussen N, Fisker R, Jensen JJ, Naredi P, Hokland M (2002) Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival. Br J Cancer 87:194

    PubMed  CAS  Google Scholar 

  21. Verra N, de Jong D, Bex A, Batchelor D, Dellemijn T, Sein J, Nooijen W, Meinhardt W, Horenblas S, de Gast G, Vyth-Dreese F (2005) Infiltration of activated dendritic cells and T cells in renal cell carcinoma following combined cytokine immunotherapy. Eur Urol 48:527

    PubMed  CAS  Google Scholar 

  22. Childs R, Chernoff A, Contentin N, Bahceci E, Schrump D, Leitman S, Read EJ, Tisdale J, Dunbar C, Linehan WM, Young NS, Barrett AJ (2000) Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med 343:750

    PubMed  CAS  Google Scholar 

  23. Rini BI, Zimmerman T, Stadler WM, Gajewski TF, Vogelzang NJ (2002) Allogeneic stem-cell transplantation of renal cell cancer after nonmyeloablative chemotherapy: feasibility, engraftment, and clinical results. J Clin Oncol 20:2017

    PubMed  Google Scholar 

  24. Roigas J, Massenkeil G (2005) Nonmyeloablative allogeneic stem cell transplantation in metastatic renal cell carcinoma: a new therapeutic option or just a clinical experiment? World J Urol 23:213

    PubMed  Google Scholar 

  25. Blaise D, Bay JO, Faucher C, Michallet M, Boiron JM, Choufi B, Cahn JY, Gratecos N, Sotto JJ, Francois S, Fleury J, Mohty M, Chabannon C, Bilger K, Gravis G, Viret F, Braud AC, Bardou VJ, Maraninchi D, Viens P (2004) Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors. Blood 103:435

    PubMed  CAS  Google Scholar 

  26. Harlin H, Artz AS, Mahowald M, Rini BI, Zimmerman T, Vogelzang NJ, Gajewski TF (2004) Clinical responses following nonmyeloablative allogeneic stem cell transplantation for renal cell carcinoma are associated with expansion of CD8+ IFN-gamma-producing T cells. Bone Marrow Transplant 33:491

    PubMed  CAS  Google Scholar 

  27. Tykodi SS, Warren EH, Thompson JA, Riddell SR, Childs RW, Otterud BE, Leppert MF, Storb R, Sandmaier BM (2004) Allogeneic hematopoietic cell transplantation for metastatic renal cell carcinoma after nonmyeloablative conditioning: toxicity, clinical response, and immunological response to minor histocompatibility antigens. Clin Cancer Res 10:7799

    PubMed  CAS  Google Scholar 

  28. Angevin E, Kremer F, Gaudin C, Hercend T, Triebel F (1997) Analysis of T-cell immune response in renal cell carcinoma: polarization to type 1-like differentiation pattern, clonal T-cell expansion and tumor-specific cytotoxicity. Int J Cancer 72:431

    PubMed  CAS  Google Scholar 

  29. Van den Hove LE, Van Gool SW, Van Poppel H, Baert L, Coorevits L, Van Damme B, Ceuppens JL (1997) Phenotype, cytokine production and cytolytic capacity of fresh (uncultured) tumour-infiltrating T lymphocytes in human renal cell carcinoma. Clin Exp Immunol 109:501

    PubMed  Google Scholar 

  30. Nakano O, Sato M, Naito Y, Suzuki K, Orikasa S, Aizawa M, Suzuki Y, Shintaku I, Nagura H, Ohtani H (2001) Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res 61:5132

    PubMed  CAS  Google Scholar 

  31. Jantzer P, Schendel DJ (1998) Human renal cell carcinoma antigen-specific CTLs: antigen-driven selection and long-term persistence in vivo. Cancer Res 58:3078

    PubMed  CAS  Google Scholar 

  32. Bernhard H, Maeurer MJ, Jager E, Wolfel T, Schneider J, Karbach J, Seliger B, Huber C, Storkus WS, Lotze MT, Meyer zum Buschenfelde KH, Knuth A (1996) Recognition of human renal cell carcinoma and melanoma by HLA-A2-restricted cytotoxic T lymphocytes is mediated by shared peptide epitopes and up-regulated by interferon-gamma. Scand J Immunol 44:285

    PubMed  CAS  Google Scholar 

  33. Mautner J, Jaffee EM, Pardoll DM (2005) Tumor-specific CD4+ T cells from a patient with renal cell carcinoma recognize diverse shared antigens. Int J Cancer 115:752

    PubMed  CAS  Google Scholar 

  34. Sahin U, Tureci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M (1995) Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci USA 92:11810

    PubMed  CAS  Google Scholar 

  35. Koroleva EP, Lagarkova MA, Mesheryakov AA, Scanlan MJ, Old LJ, Nedospasov SA, Kuprash DV (2002) Serological identification of antigens associated with renal cell carcinoma. Russ J Immunol 7:229

    PubMed  Google Scholar 

  36. Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, Gure AO, Jager D, Jager E, Knuth A, Chen YT, Old LJ (1999) Antigens recognized by autologous antibody in patients with renal-cell carcinoma. Int J Cancer 83:456

    PubMed  CAS  Google Scholar 

  37. Klade CS, Voss T, Krystek E, Ahorn H, Zatloukal K, Pummer K, Adolf GR (2001) Identification of tumor antigens in renal cell carcinoma by serological proteome analysis. Proteomics 1:890

    PubMed  CAS  Google Scholar 

  38. Devitt G, Meyer C, Wiedemann N, Eichmuller S, Kopp-Schneider A, Haferkamp A, Hautmann R, Zoller M (2005) Serological analysis of human renal cell carcinoma. Int J Cancer 118:2210

    Google Scholar 

  39. Unwin RD, Harnden P, Pappin D, Rahman D, Whelan P, Craven RA, Selby PJ, Banks RE (2003) Serological and proteomic evaluation of antibody responses in the identification of tumor antigens in renal cell carcinoma. Proteomics 3:45

    PubMed  CAS  Google Scholar 

  40. Jager E, Nagata Y, Gnjatic S, Wada H, Stockert E, Karbach J, Dunbar PR, Lee SY, Jungbluth A, Jager D, Arand M, Ritter G, Cerundolo V, Dupont B, Chen YT, Old LJ, Knuth A (2000) Monitoring CD8 T cell responses to NY-ESO-1: correlation of humoral and cellular immune responses. Proc Natl Acad Sci USA 97:4760

    PubMed  CAS  Google Scholar 

  41. Gnjatic S, Atanackovic D, Jager E, Matsuo M, Selvakumar A, Altorki NK, Maki RG, Dupont B, Ritter G, Chen YT, Knuth A, Old LJ (2003) Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: correlation with antibody responses. Proc Natl Acad Sci USA 100:8862

    PubMed  CAS  Google Scholar 

  42. Rammensee HG, Weinschenk T, Gouttefangeas C, Stevanovic S (2002) Towards patient-specific tumor antigen selection for vaccination. Immunol Rev 188:164

    PubMed  CAS  Google Scholar 

  43. Probst-Kepper M, Stroobant V, Kridel R, Gaugler B, Landry C, Brasseur F, Cosyns JP, Weynand B, Boon T, Van den Eynde BJ (2001) An alternative open reading frame of the human macrophage colony-stimulating factor gene is independently translated and codes for an antigenic peptide of 14 amino acids recognized by tumor-infiltrating CD8 T lymphocytes. J Exp Med 193:1189

    PubMed  CAS  Google Scholar 

  44. Van den Eynde BJ, Gaugler B, Probst-Kepper M, Michaux L, Devuyst O, Lorge F, Weynants P, Boon T (1999) A new antigen recognized by cytolytic T lymphocytes on a human kidney tumor results from reverse strand transcription. J Exp Med 190:1793

    Google Scholar 

  45. Ronsin C, Chung-Scott V, Poullion I, Aknouche N, Gaudin C, Triebel F (1999) A non-AUG-defined alternative open reading frame of the intestinal carboxyl esterase mRNA generates an epitope recognized by renal cell carcinoma-reactive tumor-infiltrating lymphocytes in situ. J Immunol 163:483

    PubMed  CAS  Google Scholar 

  46. Brandle D, Brasseur F, Weynants P, Boon T, Van den Eynde B (1996) A mutated HLA-A2 molecule recognized by autologous cytotoxic T lymphocytes on a human renal cell carcinoma. J Exp Med 183:2501

    PubMed  CAS  Google Scholar 

  47. Gaudin C, Kremer F, Angevin E, Scott V, Triebel F (1999) A hsp70–2 mutation recognized by CTL on a human renal cell carcinoma. J Immunol 162:1730

    PubMed  CAS  Google Scholar 

  48. Wang RF, Parkhurst MR, Kawakami Y, Robbins PF, Rosenberg SA (1996) Utilization of an alternative open reading frame of a normal gene in generating a novel human cancer antigen. J Exp Med 183:1131

    PubMed  CAS  Google Scholar 

  49. Hanada K, Yewdell JW, Yang JC (2004) Immune recognition of a human renal cancer antigen through post-translational protein splicing. Nature 427:252

    PubMed  CAS  Google Scholar 

  50. Bui MH, Visapaa H, Seligson D, Kim H, Han KR, Huang Y, Horvath S, Stanbridge EJ, Palotie A, Figlin RA, Belldegrun AS (2004) Prognostic value of carbonic anhydrase IX and KI67 as predictors of survival for renal clear cell carcinoma. J Urol 171:2461

    PubMed  Google Scholar 

  51. Atkins M, Regan M, McDermott D, Mier J, Stanbridge E, Youmans A, Febbo P, Upton M, Lechpammer M, Signoretti S (2005) Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer. Clin Cancer Res 11:3714

    PubMed  CAS  Google Scholar 

  52. Weinschenk T, Gouttefangeas C, Schirle M, Obermayr F, Walter S, Schoor O, Kurek R, Loeser W, Bichler KH, Wernet D, Stevanovic S, Rammensee HG (2002) Integrated functional genomics approach for the design of patient-individual antitumor vaccines. Cancer Res 62:5818

    PubMed  CAS  Google Scholar 

  53. Cutillas P, Burlingame A, Unwin R (2004) Proteomic strategies and their application in studies of renal function. News Physiol Sci 19:114

    PubMed  CAS  Google Scholar 

  54. Cox AL, Skipper J, Chen Y, Henderson RA, Darrow TL, Shabanowitz J, Engelhard VH, Hunt DF, Slingluff CL Jr (1994) Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. Science 264:716

    PubMed  CAS  Google Scholar 

  55. Hofmann S, Gluckmann M, Kausche S, Schmidt A, Corvey C, Lichtenfels R, Huber C, Albrecht C, Karas M, Herr W (2005) Rapid and sensitive identification of major histocompatibility complex class I-associated tumor peptides by Nano-LC MALDI MS/MS. Mol Cell Proteomics 4:1888

    PubMed  CAS  Google Scholar 

  56. Lemmel C, Weik S, Eberle U, Dengjel J, Kratt T, Becker HD, Rammensee HG, Stevanovic S (2004) Differential quantitative analysis of MHC ligands by mass spectrometry using stable isotope labeling. Nat Biotechnol 22:450

    PubMed  CAS  Google Scholar 

  57. Kruger T, Schoor O, Lemmel C, Kraemer B, Reichle C, Dengjel J, Weinschenk T, Muller M, Hennenlotter J, Stenzl A, Rammensee HG, Stevanovic S (2005) Lessons to be learned from primary renal cell carcinomas: novel tumor antigens and HLA ligands for immunotherapy. Cancer Immunol Immunother 54:826

    PubMed  Google Scholar 

  58. Kramer BF, Schoor O, Kruger T, Reichle C, Muller M, Weinschenk T, Hennenlotter J, Stenzl A, Rammensee HG, Stevanovic S (2005) MAGED4-expression in renal cell carcinoma and identification of an HLA-A*25-restricted MHC class I ligand from solid tumor tissue. Cancer Biol Ther 4:943

    Article  PubMed  Google Scholar 

  59. Schag K, Schmidt SM, Muller MR, Weinschenk T, Appel S, Weck MM, Grunebach F, Stevanovic S, Rammensee HG, Brossart P (2004) Identification of C-met oncogene as a broadly expressed tumor-associated antigen recognized by cytotoxic T-lymphocytes. Clin Cancer Res 10:3658

    PubMed  CAS  Google Scholar 

  60. Schmidt SM, Schag K, Muller MR, Weinschenk T, Appel S, Schoor O, Weck MM, Grunebach F, Kanz L, Stevanovic S, Rammensee HG, Brossart P (2004) Induction of adipophilin-specific cytotoxic T lymphocytes using a novel HLA-A2-binding peptide that mediates tumor cell lysis. Cancer Res 64:1164

    PubMed  CAS  Google Scholar 

  61. Maleno I, Lopez Nevot MA, Seliger B, Garrido F (2004) Low frequency of HLA haplotype loss associated with loss of heterozygocity in chromosome region 6p21 in clear renal cell carcinomas. Int J Cancer 109:636

    PubMed  CAS  Google Scholar 

  62. Ibrahim el C, Allory Y, Commo F, Gattegno B, Callard P, Paul P (2003) Altered pattern of major histocompatibility complex expression in renal carcinoma: tumor-specific expression of the nonclassical human leukocyte antigen-G molecule is restricted to clear cell carcinoma while up-regulation of other major histocompatibility complex antigens is primarily distributed in all subtypes of renal carcinoma. Am J Pathol 162:501

    PubMed  Google Scholar 

  63. Seliger B, Atkins D, Bock M, Ritz U, Ferrone S, Huber C, Storkel S (2003) Characterization of human lymphocyte antigen class I antigen-processing machinery defects in renal cell carcinoma lesions with special emphasis on transporter-associated with antigen-processing down-regulation. Clin Cancer Res 9:1721

    PubMed  CAS  Google Scholar 

  64. Cardi G, Heaney JA, Schned AR, Phillips DM, Branda MT, Ernstoff MS (1997) T-cell receptor zeta-chain expression on tumor-infiltrating lymphocytes from renal cell carcinoma. Cancer Res 57:3517

    PubMed  CAS  Google Scholar 

  65. Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J, McDermott D, Quiceno D, Youmans A, O’Neill A, Mier J, Ochoa AC (2005) Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res 65:3044

    PubMed  CAS  Google Scholar 

  66. Guerra N, Guillard M, Angevin E, Echchakir H, Escudier B, Moretta A, Chouaib S, Caignard A (2000) Killer inhibitory receptor (CD158b) modulates the lytic activity of tumor-specific T lymphocytes infiltrating renal cell carcinomas. Blood 95:2883

    PubMed  CAS  Google Scholar 

  67. Donskov F, von der Maase H, Marcussen N, Hamilton-Dutoit S, Madsen HH, Jensen JJ, Hokland M (2004) Fas ligand expression in metastatic renal cell carcinoma during interleukin-2 based immunotherapy: no in vivo effect of Fas ligand tumor counterattack. Clin Cancer Res 10:7911

    PubMed  CAS  Google Scholar 

  68. Thompson RH, Gillett MD, Cheville JC, Lohse CM, Dong H, Webster WS, Chen L, Zincke H, Blute ML, Leibovich BC, Kwon ED (2005) Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma. Cancer 104:2084

    PubMed  CAS  Google Scholar 

  69. Woo EY, Yeh H, Chu CS, Schlienger K, Carroll RG, Riley JL, Kaiser LR, June CH (2002) Cutting edge: regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J Immunol 168:4272

    PubMed  CAS  Google Scholar 

  70. Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B (2003) Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 9:606

    PubMed  Google Scholar 

  71. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942

    PubMed  CAS  Google Scholar 

  72. Cesana GC, DeRaffele G, Cohen S, Moroziewicz D, Mitcham J, Stoutenburg J, Cheung K, Hesdorffer C, Kim-Schulze S, Kaufman HL (2006) Characterization of CD4+CD25+ regulatory T cells in patients treated with high-dose interleukin-2 for metastatic melanoma or renal cell carcinoma. J Clin Oncol 24:1169

    PubMed  CAS  Google Scholar 

  73. Wang HY, Lee DA, Peng G, Guo Z, Li Y, Kiniwa Y, Shevach EM, Wang RF (2004) Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity 20:107

    PubMed  CAS  Google Scholar 

  74. Steffens MG, Boerman OC, De Mulder PH, Oyen WJ, Buijs WC, Witjes JA, van den Broek WJ, Oosterwijk-Wakka JC, Debruyne FM, Corstens FH, Oosterwijk E (1999) Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250. Clin Cancer Res 5:3268s

    PubMed  CAS  Google Scholar 

  75. Bleumer I, Knuth A, Oosterwijk E, Hofmann R, Varga Z, Lamers C, Kruit W, Melchior S, Mala C, Ullrich S, De Mulder P, Mulders PF, Beck J (2004) A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients. Br J Cancer 90:985

    PubMed  CAS  Google Scholar 

  76. Bleumer I, Oosterwijk E, Oosterwijk-Wakka JC, Voller MC, Melchior S, Warnaar SO, Mala C, Beck J, Mulders PF (2006) A clinical trial with chimeric monoclonal antibody WX-G250 and low dose interleukin-2 pulsing scheme for advanced renal cell carcinoma. J Urol 175:57

    PubMed  CAS  Google Scholar 

  77. Rini BI, Small EJ (2005) Biology and clinical development of vascular endothelial growth factor-targeted therapy in renal cell carcinoma. J Clin Oncol 23:1028

    PubMed  CAS  Google Scholar 

  78. Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427

    PubMed  CAS  Google Scholar 

  79. Elaraj DM, White DE, Steinberg SM, Haworth L, Rosenberg SA, Yang JC (2004) A pilot study of antiangiogenic therapy with bevacizumab and thalidomide in patients with metastatic renal cell carcinoma. J Immunother 27:259

    PubMed  CAS  Google Scholar 

  80. Hainsworth JD, Sosman JA, Spigel DR, Edwards DL, Baughman C, Greco A (2005) Treatment of metastatic renal cell carcinoma with a combination of bevacizumab and erlotinib. J Clin Oncol 23:7889

    PubMed  CAS  Google Scholar 

  81. Rini BI, Halabi S, Taylor J, Small EJ, Schilsky RL (2004) Cancer and Leukemia Group B 90206: a randomized phase III trial of interferon-alpha or interferon-alpha plus anti-vascular endothelial growth factor antibody (bevacizumab) in metastatic renal cell carcinoma. Clin Cancer Res 10:2584

    PubMed  CAS  Google Scholar 

  82. Rowinsky EK, Schwartz GH, Gollob JA, Thompson JA, Vogelzang NJ, Figlin R, Bukowski R, Haas N, Lockbaum P, Li YP, Arends R, Foon KA, Schwab G, Dutcher J (2004) Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer. J Clin Oncol 22:3003

    PubMed  CAS  Google Scholar 

  83. Motzer RJ, Amato R, Todd M, Hwu WJ, Cohen R, Baselga J, Muss H, Cooper M, Yu R, Ginsberg MS, Needle M (2003) Phase II trial of antiepidermal growth factor receptor antibody C225 in patients with advanced renal cell carcinoma. Invest New Drugs 21:99

    PubMed  CAS  Google Scholar 

  84. Topalian SL, Solomon D, Avis FP, Chang AE, Freerksen DL, Linehan WM, Lotze MT, Robertson CN, Seipp CA, Simon P (1988) Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study. J Clin Oncol 6:839

    PubMed  CAS  Google Scholar 

  85. Bukowski RM, Sharfman W, Murthy S, Rayman P, Tubbs R, Alexander J, Budd GT, Sergi JS, Bauer L, Gibson V (1991) Clinical results and characterization of tumor-infiltrating lymphocytes with or without recombinant interleukin 2 in human metastatic renal cell carcinoma. Cancer Res 51:4199

    PubMed  CAS  Google Scholar 

  86. Figlin RA, Pierce WC, Kaboo R, Tso CL, Moldawer N, Gitlitz B, deKernion J, Belldegrun A (1997) Treatment of metastatic renal cell carcinoma with nephrectomy, interleukin-2 and cytokine-primed or CD8(+) selected tumor infiltrating lymphocytes from primary tumor. J Urol 158:740

    PubMed  CAS  Google Scholar 

  87. Figlin RA, Thompson JA, Bukowski RM, Vogelzang NJ, Novick AC, Lange P, Steinberg GD, Belldegrun AS (1999) Multicenter, randomized, phase III trial of CD8(+) tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J Clin Oncol 17:2521

    PubMed  CAS  Google Scholar 

  88. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA (2002) Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298:850

    PubMed  CAS  Google Scholar 

  89. Jocham D, Richter A, Hoffmann L, Iwig K, Fahlenkamp D, Zakrzewski G, Schmitt E, Dannenberg T, Lehmacher W, von Wietersheim J, Doehn C (2004) Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial. Lancet 363:594

    PubMed  CAS  Google Scholar 

  90. Zhou X, Jun do Y, Thomas AM, Huang X, Huang LQ, Mautner J, Mo W, Robbins PF, Pardoll DM, Jaffee EM (2005) Diverse CD8+ T-cell responses to renal cell carcinoma antigens in patients treated with an autologous granulocyte-macrophage colony-stimulating factor gene-transduced renal tumor cell vaccine. Cancer Res 65:1079

    PubMed  CAS  Google Scholar 

  91. Tani K, Azuma M, Nakazaki Y, Oyaizu N, Hase H, Ohata J, Takahashi K, OiwaMonna M, Hanazawa K, Wakumoto Y, Kawai K, Noguchi M, Soda Y, Kunisaki R, Watari K, Takahashi S, Machida U, Satoh N, Tojo A, Maekawa T, Eriguchi M, Tomikawa S, Tahara H, Inoue Y, Yoshikawa H, Yamada Y, Iwamoto A, Hamada H, Yamashita N, Okumura K, Kakizoe T, Akaza H, Fujime M, Clift S, Ando D, Mulligan R, Asano S (2004) Phase I study of autologous tumor vaccines transduced with the GM-CSF gene in four patients with stage IV renal cell cancer in Japan: clinical and immunological findings. Mol Ther 10:799

    PubMed  CAS  Google Scholar 

  92. Gitlitz BJ, Belldegrun AS, Zisman A, Chao DH, Pantuck AJ, Hinkel A, Mulders P, Moldawer N, Tso CL, Figlin RA (2003) A pilot trial of tumor lysate-loaded dendritic cells for the treatment of metastatic renal cell carcinoma. J Immunother 26:412

    PubMed  Google Scholar 

  93. Marten A, Flieger D, Renoth S, Weineck S, Albers P, Compes M, Schottker B, Ziske C, Engelhart S, Hanfland P, Krizek L, Faber C, Von Ruecker A, Muller S, Sauerbruch T, Schmidt-Wolf IG (2002) Therapeutic vaccination against metastatic renal cell carcinoma by autologous dendritic cells: preclinical results and outcome of a first clinical phase I/II trial. Cancer Immunol Immunother 51:637

    PubMed  Google Scholar 

  94. Holtl L, Zelle-Rieser C, Gander H, Papesh C, Ramoner R, Bartsch G, Rogatsch H, Barsoum AL, Coggin JH Jr, Thurnher M (2002) Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin Cancer Res 8:3369

    PubMed  CAS  Google Scholar 

  95. Oosterwijk-Wakka JC, Tiemessen DM, Bleumer I, De Vries IJ, Jongmans W, Adema GJ, Debruyne FM, De Mulder PH, Oosterwijk E, Mulders PF (2002) Vaccination of patients with metastatic renal cell carcinoma with autologous dendritic cells pulsed with autologous tumor antigens in combination with interleukin-2: a phase 1 study. J Immunother 25:500

    PubMed  CAS  Google Scholar 

  96. Su Z, Dannull J, Heiser A, Yancey D, Pruitt S, Madden J, Coleman D, Niedzwiecki D, Gilboa E, Vieweg J (2003) Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells. Cancer Res 63:2127

    PubMed  CAS  Google Scholar 

  97. Frankenberger B, Regn S, Geiger C, Noessner E, Falk CS, Pohla H, Javorovic M, Silberzahn T, Wilde S, Buchner A, Siebels M, Oberneder R, Willimsky G, Pezzutto A, Blankenstein T, Schendel DJ (2005) Cell-based vaccines for renal cell carcinoma: genetically-engineered tumor cells and monocyte-derived dendritic cells. World J Urol 23:166

    PubMed  CAS  Google Scholar 

  98. Holtl L, Ramoner R, Zelle-Rieser C, Gander H, Putz T, Papesh C, Nussbaumer W, Falkensammer C, Bartsch G, Thurnher M (2005) Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma with or without cyclophosphamide. Cancer Immunol Immunother 54:663

    PubMed  Google Scholar 

  99. Marten A, Renoth S, Heinicke T, Albers P, Pauli A, Mey U, Caspari R, Flieger D, Hanfland P, Von Ruecker A, Eis-Hubinger AM, Muller S, Schwaner I, Lohmann U, Heylmann G, Sauerbruch T, Schmidt-Wolf IG (2003) Allogeneic dendritic cells fused with tumor cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma. Hum Gene Ther 14:483

    PubMed  Google Scholar 

  100. Wierecky J, Mueller M, Brossart P (2006) Dendritic cell-based cancer immunotherapy targeting MUC-1. Cancer Immunol Immunother 55:63

    PubMed  CAS  Google Scholar 

  101. Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, Restifo NP, Haworth LR, Seipp CA, Freezer LJ, Morton KE, Mavroukakis SA, Duray PH, Steinberg SM, Allison JP, Davis TA, Rosenberg SA (2003) Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci USA 100:8372

    PubMed  CAS  Google Scholar 

  102. Dannull J, Su Z, Rizzieri D, Yang BK, Coleman D, Yancey D, Zhang A, Dahm P, Chao N, Gilboa E, Vieweg J (2005) Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest 115:3623

    PubMed  CAS  Google Scholar 

  103. Alves PM, Faure O, Graff-Dubois S, Gross DA, Cornet S, Chouaib S, Miconnet I, Lemonnier FA, Kosmatopoulos K (2003) EphA2 as target of anticancer immunotherapy: identification of HLA-A*0201-restricted epitopes. Cancer Res 63:8476

    PubMed  CAS  Google Scholar 

  104. Tatsumi T, Herrem CJ, Olson WC, Finke JH, Bukowski RM, Kinch MS, Ranieri E, Storkus WJ (2003) Disease stage variation in CD4+ and CD8+ T-cell reactivity to the receptor tyrosine kinase EphA2 in patients with renal cell carcinoma. Cancer Res 63:4481

    PubMed  CAS  Google Scholar 

  105. Kobayashi H, Wood M, Song Y, Appella E, Celis E (2000) Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen. Cancer Res 60:5228

    PubMed  CAS  Google Scholar 

  106. Perez SA, Sotiropoulou PA, Sotiriadou NN, Mamalaki A, Gritzapis AD, Echner H, Voelter W, Pawelec G, Papamichail M, Baxevanis CN (2002) HER-2/neu-derived peptide 884–899 is expressed by human breast, colorectal and pancreatic adenocarcinomas and is recognized by in-vitro-induced specific CD4(+) T cell clones. Cancer Immunol Immunother 50:615

    PubMed  CAS  Google Scholar 

  107. Chikamatsu K, Albers A, Stanson J, Kwok WW, Appella E, Whiteside TL, DeLeo AB (2003) P53(110–124)-specific human CD4+ T-helper cells enhance in vitro generation and antitumor function of tumor-reactive CD8+ T cells. Cancer Res 63:3675

    PubMed  CAS  Google Scholar 

  108. Rojas JM, McArdle SE, Horton RB, Bell M, Mian S, Li G, Ali SA, Rees RC (2005) Peptide immunisation of HLA-DR-transgenic mice permits the identification of a novel HLA-DRbeta1*. Cancer Immunol Immunother 54:243

    PubMed  CAS  Google Scholar 

  109. Fujita H, Senju S, Yokomizo H, Saya H, Ogawa M, Matsushita S, Nishimura Y (1998) Evidence that HLA class II-restricted human CD4+ T cells specific to p53 self peptides respond to p53 proteins of both wild and mutant forms. Eur J Immunol 28:305

    PubMed  CAS  Google Scholar 

  110. Andersen MH, Pedersen LO, Capeller B, Brocker EB, Becker JC, thor SP (2001) Spontaneous cytotoxic T-cell responses against survivin-derived MHC class I-restricted T-cell epitopes in situ as well as ex vivo in cancer patients. Cancer Res 61:5964

    PubMed  CAS  Google Scholar 

  111. Hirohashi Y, Torigoe T, Maeda A, Nabeta Y, Kamiguchi K, Sato T, Yoda J, Ikeda H, Hirata K, Yamanaka N, Sato N (2002) An HLA-A24-restricted cytotoxic T lymphocyte epitope of a tumor-associated protein, survivin. Clin Cancer Res 8:1731

    PubMed  CAS  Google Scholar 

  112. Reker S, Becker JC, Svane IM, Ralfkiaer E, Straten PT, Andersen MH (2004) HLA-B35-restricted immune responses against survivin in cancer patients. Int J Cancer 108:937

    PubMed  CAS  Google Scholar 

  113. Schroers R, Shen L, Rollins L, Rooney CM, Slawin K, Sonderstrup G, Huang XF, Chen SY (2003) Human telomerase reverse transcriptase-specific T-helper responses induced by promiscuous major histocompatibility complex class II-restricted epitopes. Clin Cancer Res 9:4743

    PubMed  CAS  Google Scholar 

  114. Schultz ES, Chapiro J, Lurquin C, Claverol S, Burlet-Schiltz O, Warnier G, Russo V, Morel S, Levy F, Boon T, Van den Eynde BJ, van der Bruggen P (2002) The production of a new MAGE-3 peptide presented to cytolytic T lymphocytes by HLA-B40 requires the immunoproteasome. J Exp Med 195:391

    PubMed  CAS  Google Scholar 

  115. Consogno G, Manici S, Facchinetti V, Bachi A, Hammer J, Conti-Fine BM, Rugarli C, Traversari C, Protti MP (2003) Identification of immunodominant regions among promiscuous HLA-DR-restricted CD4+ T-cell epitopes on the tumor antigen MAGE-3. Blood 101:1038

    PubMed  CAS  Google Scholar 

  116. Oehlrich N, Devitt G, Linnebacher M, Schwitalle Y, Grosskinski S, Stevanovic S, Zoller M (2005) Generation of RAGE-1 and MAGE-9 peptide-specific cytotoxic T-lymphocyte lines for transfer in patients with renal cell carcinoma. Int J Cancer 117:256

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We wish to thank Lynne Yakes for assistance in preparing the manuscript. The authors were supported by a grant from the Ludwig Hiermaier foundation, Tübingen, by the Deutsche Forschungsgemeinschaft (DFG, SFB 685) and by the European Union (Allostem and Cancerimmunotherapy grants).

Author information

Authors and Affiliations

  1. Institute for Cell Biology, Department of Immunology, Eberhard Karls University, Auf der Morgenstelle 15, 72076, Tubingen, Germany

    Cécile Gouttefangeas, Stefan Stevanović & Hans-Georg Rammensee

  2. Clinic for Urology, Eberhard Karls University, Tubingen, Germany

    Arnulf Stenzl

Authors
  1. Cécile Gouttefangeas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arnulf Stenzl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefan Stevanović
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hans-Georg Rammensee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cécile Gouttefangeas.

Additional information

This article is a symposium paper from the conference “Progress in Vaccination against Cancer 2005 (PIVAC 5)”, held in Athens, Greece, on 20–21 September 2005.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gouttefangeas, C., Stenzl, A., Stevanović, S. et al. Immunotherapy of renal cell carcinoma. Cancer Immunol Immunother 56, 117–128 (2007). https://doi.org/10.1007/s00262-006-0172-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-006-0172-4

Keywords

Search

Navigation