Vaccination therapy in renal cell carcinoma: Current position and future options in metastatic and localized disease

Expert Review of Vaccines

Volumn 10, Issue 6, 2011, Pages 837-852

  Brookman May, Sabine ^a   Burger, Maximilian ^a   Wieland, Wolf F ^a   Rößler, Wolfgang ^a   May, Matthias ^a   Denzinger, Stefan ^a  

^a UNIVERSITY OF REGENSBURG   (Germany)

Author keywords

autologous tumor cell vaccine; dendritic cell based vaccine; genetically modified vaccine; immunomodulation; peptide based vaccine; renal cell carcinoma; vaccination therapy

Indexed keywords

ALPHA INTERFERON; ALPHA2A INTERFERON; ANTIGEN; ANTINEOPLASTIC AGENT; BCG VACCINE; BETA INTERFERON; CARBONATE DEHYDRATASE IX; CYCLOPHOSPHAMIDE; DENDRITIC CELL VACCINE; FREUND ADJUVANT; GIRENTUXIMAB; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HLA A2402 ANTIGEN; IMA 901; INTERLEUKIN 12; INTERLEUKIN 2; KEYHOLE LIMPET HEMOCYANIN; MODIFIED VACCINIA VIRUS ANKARA 5T4 VACCINE; MONTANIDE ISA 51; OLIGONUCLEOTIDE; PLACEBO; RENIALE; SRL 172; SUNITINIB; TUMOR CELL VACCINE; UNCLASSIFIED DRUG; VITESPEN; WT1 PROTEIN; WXG 250;

CANCER ADJUVANT THERAPY; CANCER IMMUNOTHERAPY; CANCER TRANSPLANTATION; DRUG TARGETING; GENETIC MODEL; HUMAN; IMMUNE RESPONSE; KIDNEY CARCINOMA; LEUKOPENIA; LOW DRUG DOSE; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; UNSPECIFIED SIDE EFFECT;

CANCER VACCINES; CARCINOMA, RENAL CELL; CLINICAL TRIALS AS TOPIC; HUMANS; NEOPLASM METASTASIS; TREATMENT OUTCOME;

EID: 79959568681     PISSN: 14760584     EISSN: 17448395     Source Type: Journal    
DOI: 10.1586/erv.11.64     Document Type: Review

References (110)

1. Ljungberg B, Hanbury DC, Kuczyk MA et al. Renal cell carcinoma guideline. Eur. Urol. 51, 1502-1510 (2007 (Pubitemid 46634775)
2. Ritchie AWS, de Kernion JB. The natural history and clinical features of renal cell carcinoma. Semin. Nephrol. 7, 131-139 (1987
3. Tykkä H, Hjelt L, Oravisto KJ, Turunen M, Tallberg T. Disappearance of lung metastases during immunotherapy in five patients suffering from renal carcinoma. Scand. J. Respir. Dis. Suppl. 89, 123-134 (1974
4. Berntsen A, Geertsen PF, Svane IM et al. Therapeutic dendritic cell vacciniation of patients with renal cell carcinoma. Eur. Urol. 50, 34-43 (2006 (Pubitemid 43850125)
5. Frankenberger B, Regn S, Geiger C et al. Cell-based vaccines for renal cell carcinoma: genetically-engineered tumor cells and moncyte-derived dencritic cells. World J. Urol. 23, 166-174 (2005 (Pubitemid 41136037)
6. Escudier B, Eisen T, Stadler WM et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med. 356(2), 125-134 (2007 (Pubitemid 46089673)
7. Escudier B, Pluzanska A, Koralewski P et al. Bevacizumab plus interferon alpha-2a for treatment of metastatic renal cell carcinoma: a randomized, double-blind Phase III trial. Lancet 370(9605), 2103-2111 (2007 (Pubitemid 350296300)
8. Motzer RJ, Hutson TE, Tomczak P et al. Sunitinib versus interferon a in metastatic renal-cell carcinoma. N. Engl. J. Med. 356(2), 115-124 (2007 (Pubitemid 46089672)
9. Hudes G, Carducci M, Tomczak P et al. Temsirolimus, interferon a, or both for advanced renal-cell carcinoma. N. Engl. J. Med. 356(22), 2271-2281 (2007 (Pubitemid 46849157)
10. Motzer RJ, Escudier B, Oudard S et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled Phase III trial. Lancet 372(9637), 449-456 (2008
11. Uemura H, De Valesco MA. Tumor vaccines in renal cell carcinoma. World J. Urol. 26, 147-154 (2008
12. Brossart P, Stuhler G, Flad T et al. Her-2/ neu-derived peptides are tumor-associated antigens expressed by human renal cell and colon carcinoma lines and are recognized by in vitro induced specific cytotoxic T lymphocytes. Cancer Res. 58(4), 732-736 (1998 (Pubitemid 28099485)
13. Flad T, Spengler B, Kalbacher H et al. Direct identification of major histocompatibility complex class I-bound tumor-associated peptide antigens of a renal carcinoma cell line by a novel mass spectrometric method. Cancer Res. 58(24), 5803-5811 (1998 (Pubitemid 29006422)
14. Neumann E, Engelsberg A, Decker J et al. Heterogeneous expression of the tumor-associated antigens RAGE-1, PRAME, and glycoprotein 75 in human renal cell carcinoma: candidates for T-cell-based immunotherapies? Cancer Res. 58(18), 4090-4095 (1998 (Pubitemid 28440562)
15. Vissers JL, De Vries IJ, Schreurs MW et al. The renal cell carcinoma-associated antigen G250 encodes a human leukocyte antigen (HLA)-A2.1-restricted epitope recognized by cytotoxic T lymphocytes. Cancer Res. 59(21), 5554-5559 (1998
16. Tso CL, Zisman A, Pantuck A et al. Induction of G250-targeted and T-cell-mediated antitumor activity against renal cell carcinoma using a chimeric fusion protein consisting of G250 and granulocyte/monocyte-colony stimulating factor. Cancer Res. 61(21), 7925-7933 (2001 (Pubitemid 33049383)
17. Uemura H, Fujimoto K, Tanaka M et al. A Phase I trial of vaccination of CA9- derived peptides for HLA-A24-positive patients with cytokine-refractory metastatic renal cell carcinoma. Clin. Cancer Res. 12(6), 1768-1775 (2006
18. Iiyama T, Udaka K, Takeda S et al. WT1 (Wilms' tumor 1) peptide immunotherapy for renal cell carcinoma. Microbiol. Immunol. 51(5), 519-530 (2007 (Pubitemid 46799719)
19. Amato RJ. Vaccine therapy for renal cell carcinoma. Rev. Urol. 5(2), 65-71 (2003
20. Avigan D. Dendritic cell/tumour fusions vaccine. Dev. Biol. (Basel) 116, 161-168 (2004
21. Kübler H, Vieweg J. Vaccines in renal cell carcinoma. Semin. Oncol. 33, 614-624 (2006 (Pubitemid 44511981)
22. Ranieri E, Gignate M, Storkus WJ, Gesualdo L. Translational mini-review series on vaccines: dendritic cell-based vaccines in renal cancer. Clin. Exp. Immunol. 147, 395-400 (2007 (Pubitemid 46208039)
23. Ernstoff MS, Crocenzi TS, Seigne JD et al. Developing a rational tumor vaccine therapy for renal cell carcinoma: immune yin and yang. Clin. Cancer Res. 13, 733-740 (2007
24. Van Poppel H, Joniau S, Van Gool S. Vaccine therapy in patients with renal cell carcinoma. Eur. Urol. 55, 1333-1344 (2009
25. Höltl L, Rieser C, Papesh C et al. Cellular and humoral immune responses in patients with metastatic renal cell carcinoma after vaccination with antigen pulsed dendritic cells. J. Urol. 161, 777-782 (1999 (Pubitemid 29422365)
26. Höltl L, Zelle-Rieser C, Gander H et al. Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin. Cancer Res. 8, 3369-3376 (2002 (Pubitemid 35340710)
27. Motzer RJ, Bander NH, Nanus DM. Sunitinib versus interferon a in metastatic renal cell carcinoma. N. Engl. J. Med. 356, 115-124 (2007 (Pubitemid 46089672)
28. Barbuto JA, Ensina LF, Neves AR et al. Dendritic cell-tumor cell hybrid vaccination for metastatic cancer. Cancer Immunol. Immunother. 54, 663-670 (2005
29. Wierecky J, Müller MR, Wirths S et al. Immunologic and clinical responses after vaccinations with peptide-pulsed dendritic cells in metastatic renal cancer patients. Cancer Res. 66, 5910-5918 (2006 (Pubitemid 43927146)
30. Kim JH, Lee Y, Bae YS et al. Phase I/II study of immunotherapy using autologous tumor lysate-pulsed dendritic cells in patients with metastatic renal cell carcinoma. Clin. Immunol. 125(3), 257-267 (2007 (Pubitemid 350116707)
31. Bleumer I, Tiemessen DM, Oosterwijk- Wakka JC et al. Preliminary analysis of patients with progressive renal cell carcinoma vaccinated with CA9-peptide-pulsed mature dendritic cells. J. Immunother. 30(1), 116-122 (2007). (Pubitemid 46052210)
32. Matsumoto A, Haraguchi K, Takahashi T et al. Immunotherapy against metastatic renal cell carcinoma with mature dendritic cells. Int. J. Urol. 14(4), 277-283 (2007 (Pubitemid 46669054)
33. Avigan DE, Vasir B, George DJ et al. Phase I/II study of vaccination with electrofused allogeneic dendritic cells/autologous tumor-derived cells in patients with stage IV renal cell carcinoma. J. Immunother. 30(7), 749-761 (2007 (Pubitemid 47480758)
34. Wei YC, Sticca RP, Li J et al. Combined treatment of dendritoma vaccine and low-dose interleukin-2 in stage IV renal cell carcinoma patients induced clinical response: a pilot study. Oncol. Rep. 18(3), 665-671 (2007
35. Oosterwijk-Wakka JC, Tiemessen DM, Bleumer I et al. Vaccination of patients with metastatic renal cell carcinoma with autologous dendritic cells pulsed with autologous tumor antigens in combination with interleukin-2: a Phase I study. J. Immunother. 25, 500-508 (2002
36. Soleimani A, Berntsen A, Svanet IM, Pederson AE. Immune responses in patients with metastatic renal cell carcinoma treated with dendritic cells pulsed with tumor lysate. Scand. J. Immunol. 70(5), 481-489 (2009
37. Schwaab T, Schwarzer A, Wolf B et al. Clinical and immunologic effects of intranodal autologous tumor lysate-dendritic cell vaccine with aldesleukin (interleukin 2) and IFN-a2a therapy in metastatic renal cell carcinoma patients. Clin. Cancer Res. 15(15), 4986-4992 (2009
38. Oki Y, Younes A. Heat shock protein-based cancer vaccines. Expert Rev. Vaccines 3, 403-411 (2004 (Pubitemid 39061705)
39. Guida M, Colluci G. Immunotherapy for metastatic renal cell carcinoma: is it a therapeutic option yet? Ann. Oncol. 18, 149-152 (2007
40. Kurth KH, Marquet R, Zwartendijk J, Warnaar SO. Autologous anticancer antigen preparation for specific immunotherapy in advanced renal cell carcinoma. Eur. Urol. 13, 103-109 (1987 (Pubitemid 17067210)
41. McCune CS, Schapira DV, Henshaw EC. Specific immunotherapy of advanced renal carcinoma: evidence for the polyclonality of metastases. Cancer 47, 1984-1987 (1981 (Pubitemid 11153435)
42. Schärfe T, Müller S, Riedmiller H et al. Jacobi GH, Hohenfellner R. Immunotherapy of metastasizing renal cell carcinoma. Results of a multicentered trial. Urol. Int. 44, 1-4 (1989 (Pubitemid 19110342)
43. Galligioni E, Quaia M, Merlo A et al. Adjuvant immunotherapy treatment of renal carcinoma patients with autologous tumor cells and bacillus Calmette-Guèrin: five-year results of a prospective randomized study. Cancer 77(12), 2560-2566 (1996
44. Schwaab T, Heaney JA, Schned AR et al. A randomized Phase II trial comparing two different sequence combinations of autologous vaccine and human recombinant interferon gamma and human recombinant interferon alpha2B therapy in patients with metastatic renal cell carcinoma: clinical outcome and analysis of immunological parameters. J. Urol. 163, 1322-1327 (2000 (Pubitemid 30169433)
45. Jocham D, Richter A, Hoffmann L et al. 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, 594-599 (2004 (Pubitemid 38264176)
46. Dillman R, Barth N, Vandermolen L et al. Autologous tumor cell line-derived vaccine for patient-specific treatment of advanced renal cell carcinoma. Cancer Biother. Radiopharm. 19(5), 570-580 (2004 (Pubitemid 39546296)
47. Dudek AZ, Mescher MF, Okazaki I et al. Autologous large multivalent immunogen vaccine in patients with metastatic melanoma and renal cell carcinoma. Am. J. Clin. Oncol. 31(2), 173-181 (2008 (Pubitemid 351519170)
48. Repmann R, Wagner S, Richter A. Adjuvant therapy of renal cell carcinoma with active-specific-immunotherapy (ASI) using autologous tumor cell lysate vaccine. Anticancer Res. 17, 2879-2882 (1997 (Pubitemid 27434810)
49. Doehn C, Richter A, Theodor RA et al. An adjuvant vaccination with Reniale prolongs survival in patients with RCC following radical nephrectomy: secondary analysis of a multicenter Phase-III trial. J. Urol. 177(Suppl.), 167 (2007) (Abstract 500
50. Doehn C, Esser N, Pauels HG et al. Mode-of-actin, efficacy, and safety of a homologous multi-epitope vaccine in a murine model for adjuvant treatment of renal cell carcinoma. Eur. Urol. 56(1), 123-131 (2009
51. May M, Kendel F, Hoschke B et al. Adjuvant autologous tumour cell vaccination in patients with renal cell carcinoma. Overall survival analysis with a follow-up period in excess of more than 10 years. Urologe A 48(9), 1075-1083 (2009
52. Frankenberger B, Regn S, Geiger C et al. Cell-based vaccines for renal cell carcinoma: genetically-engineered tumor cells and monocyte-derived dendritic cells. World J. Urol. 23(3), 166-174 (2005 (Pubitemid 41136037)
53. Simons JW, Jaffee EM, Weber CE et al. Bioactivity of autologous irradiated renal cell carcinoma vaccines generated by ex vivo granulocyte-macrophage colony-stimulating factor gene transfer. Cancer Res. 57(8), 1537-1546 (1997 (Pubitemid 27175572)
54. Antonia SJ, Seigne J, Diaz J et al. Phase I trial of a B7-1 (CD80) gene modified autologous tumor cell vaccine in combination with systemic interleukin-2 in patients with metastatic renal cell carcinoma. J. Urol. 167(5), 1995-2000 (2002 (Pubitemid 34309645)
55. Pizza G, De Vinci C, Lo Conte G et al. Allogeneic gene-modified tumour cells in metastatic kidney cancer. Report II. Folia Biol. (Praha) 50(6), 175-183 (2004 (Pubitemid 40220741)
56. Fishman M, Hunter TB, Soliman H et al. Phase II trial of B7-1 (CD-86) transduced, cultured autologous tumor cell vaccine plus subcutaneous interleukin-2 for treatment of stage IV renal cell carcinoma. J. Immunother. 31(1), 72-80 (2008 (Pubitemid 351619406)
57. Liao SY, Brewer C, Závada J et al. Identification of the MN antigen as a diagnostic biomarker of cervical intraepithelial squamous and glandular neoplasia and cervical carcinomas. Am. J. Pathol. 145(3), 598-609 (1994 (Pubitemid 24285967)
58. Saarnio J, Parkkila S, Parkkila AK et al. Immunohistochemical study of colorectal tumors for expression of a novel transmembrane carbonic anhydrase, MN/ CA IX, with potential value as a marker of cell proliferation. Am. J. Pathol. 153(1), 279-285 (1998 (Pubitemid 28317531)
59. Saarnio J, Parkkila S, Parkkila AK et al. Immunohistochemistry of carbonic anhydrase isozyme IX (MN/CA IX) in human gut reveals polarized expression in the epithelial cells with the highest proliferative capacity. J. Histochem. Cytochem. 46(4), 497-504 (1998 (Pubitemid 28158469)
60. Turner JR, Odze RD, Crum CP et al. MN antigen expression in normal, preneoplastic, and neoplastic esophagus: a clinicopathological study of a new cancer-associated biomarker. Hum. Pathol. 28(6), 740-744 (1997 (Pubitemid 27258429)
61. Swinson DE, Jones JL, Richardson D et al. Carbonic anhydrase IX expression, a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer. J. Clin. Oncol. 21(3), 473-482 (2003 (Pubitemid 46613490)
62. Gouttefangeas C, Stenzl A, Stevanovic S, Rammensee HG. Immunotherapy of renal cell carcinoma. Cancer Immunol. Immunother. 56(1), 117-128 (2007 (Pubitemid 44812454)
63. Suekane S, Nishitani M, Noguchi M et al. Phase I trial of personalized peptide vaccination for cytokine-refractory metastatic renal cell carcinoma patients. Cancer Sci. 98(12), 1965-1968 (2007 (Pubitemid 350002204)
64. Patel PM, Sim S, O'Donnell DO et al. An evaluation of a preparation of Mycobacterium vaccae (SRL172) as an immunotherapeutic agent in renal cancer. Eur. J. Cancer 44(2), 216-223 (2008
65. Vieweg J, Jackson A. Antigenic targets for renal cell carcinoma immunotherapy. Expert Opin. Biol. Ther. 4(11), 1791-1801 (2004 (Pubitemid 39518112)
66. Elkord E, Shablak A, Stern PL, Hawkins RE. 5T4 as a target for immunotherapy in renal cell carcinoma. Expert Rev. Anticancer Ther. 9(12), 1705-1709 (2009
67. Ward CM, Barrow K, Woods AM, Stern PL. The 5T4 oncofetal antigen is an early differentiation marker of mouse ES cells and its absence is s useful means to assess pluripotency. J. Cell Sci. 116, 4533-4542 (2003 (Pubitemid 37461608)
68. Ward CM, Easthem AM, Stern PL. Cell surface 5T4 antigen is transiently upregulated during early human embryonic stem cell differentiation: effect of 5T4 phenotype on neural lineage formation. Exp. Cell Res. 312, 1713-1726 (2006 (Pubitemid 43776010)
69. Amato RJ, Shingler W, Stuart N et al. Vaccination of renal cell cancer patients with modified vaccinia Ankara delivering tumor antigen 5T4 (Trovax) administered with Interleukin 2: a Phase II trial. Clin. Cancer Res. 14(22), 7504-7510 (2008
70. Kim DW, Krishnamurthy V, Bines SD, Kaufman HL. Trovax, a recombinant modified vaccinia Ankara virus encoding 5T4. Lessons learned and future development. Hum. Vaccin. 10, 1-8 (2010
71. Hawkins R, Harrop R, Naylor S et al. TRIST: a randomised, double blind, placebo controlled Phase III study of MVA-5T4 in metastatic renal cancer. Presented at: Joint ECCO 15th - 34th ESMO Multidisciplinary Congress. Berlin, Germany, 20-24 September 2009.
72. Rahma OE, Ashtar E, Ibrahim R et al. A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic renal cell carcinoma. J. Transl. Med. 8, 8 (2010
73. Brugger W, Zdrojowy R, Pluzanska A et al. Survival update of a randomized Phase 2 study (IMA901-202) investigating therapeutic vaccination with multiple tumor-associated peptides (TUMAP) in renal cell carcinoma (RCC) patients after failure of previous therapy with cytokines or kinase inhibitors. Presented at: 35th ESMO Congress. Milan, Italy, 8-12 October 2010.
74. Singh H, Hilf N, Mendrzyk R et al. Correlation of immune responses with survival in a randomized Phase II study investigating multi-TUMAP vaccinations with IMA901 plus/minus low-dose cyclophosphamide in advanced renal cell carcinoma (RCCPrograms and Abstracts of the American Society of Clinical Oncology. Chicago, IL, USA, 4-8 June 2010 (Abstract 258
75. Reinhardt C, Zdrojowy R, Szczylik C et al. Results of a ranomized Phase 2 study investigating multi-peptide vaccination with IMA901 in advanced renall cell carcinoma (RCCPresented at: American Society of Clinical Oncology. Chicago, IL, USA, 4-8 June 2010.
76. Wood C, Srivastava P, Bukowski R et al. An adjuvant autologous therapeutic vaccine (HSPCC-96; vitespen) versus observation alone for patients at high-risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised Phase III trial. Lancet 372, 145-154 (2008
77. Jonasch E, Wood C, Tamboli P et al. Vaccination of metastatic renal cell carcinoma patients with autologous tumour-derived vitespen vaccine: clinical findings. Br. J. Cancer 98, 1336-1341 (2008 (Pubitemid 351543568)
78. Kim HL, Sun X, Subjeck JR, Wang XY. Evaluation of renal cell carcinoma vaccines targeting carbonic anhydrase IX using heat shock protein 110. Cancer Immunol. Immunother. 56, 1097-1105 (2007 (Pubitemid 46675302)
79. Oosterwijk E, Ruiter DJ, Hoedemaeker PJ et al. Monoclonal antibody G250 recognizes a determinant present in renal-cell carcinoma and absent from normal kidney. Int. J. Cancer 38, 489-494 (1986 (Pubitemid 16006918)
80. Liao SY, Aurelio ON, Jan K, Zavada J, Stanbridge EJ. Identification of the MN/ CA9 protein as a reliable diagnostic biomarker of clear cell carcinoma of the kidney. Cancer Res. 57, 2827-2831 (1997 (Pubitemid 27315020)
81. Liu Z, Smyth FE, Renner C, Lee FT, Oosterwijk E, Scott AM. Anti-renal cell carcinoma chimeric antibody G250. Cytokine enhancement of in vitro antibody-dependent cellular cytotoxicity. Cancer. Immunol. Immunother. 51, 171-177 (2002 (Pubitemid 34298113)
82. Bevan P, Mala C, Kindler M, Siebels M, Oberneder R, Beck HJ. Results of a Phase I/II study with monoclonal antibody CG250 in combinaton with IFNa-2A in metastatic renal cellcarcinoma patients. J. Clin. Oncol. 22(14S), 4606 (2004
83. Oosterwijk E, Divgi CR, Brouwers A et al. Monoclonal antibody-based therapy for renal cell carcinoma. Urol. Clin. North Am. 30, 623-631 (2003 (Pubitemid 37059567)
84. Shuch B, Li Z, Belldegrun AS. Carbonic anhydrase IX and renal cell carcinoma: prognosis, response to systemic therapy, and future vaccine strategies. BJU Int. 101(Suppl. 4), 25-30 (2008
85. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat. Immunol. 3(11), 991-998 (2002 (Pubitemid 35363648)
86. Cesana GC, DeRaffele G, Cohen S et al. 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, 1169-1177 (2006 (Pubitemid 46638815)
87. Takahashi T, Kuniyasu Y, Toda M et al. Immnologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmne disease by breaking their anergic/suppressive state. Int. Immunol. 10, 1969-1980 (1998 (Pubitemid 28566059)
88. Parmiani G, Castelli C, Dalerba P et al. Cancer immunotherapy with peptide-based vaccines: what have we achieved? Where are we going? J. Natl Cancer. Inst. 94(11), 805-818 (2002 (Pubitemid 34705052)
89. Dannull J, Su Z, Rizzieri D et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J. Clin. Invest. 115, 3623-3633 (2005 (Pubitemid 43121851)
90. Höltl L, Ramoner R, Zelle-Rieser C et al. Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma with or without cyclophophamide. Cancer Immunol. Immunother. 54, 663-670 (2005 (Pubitemid 40884162)
91. Brahmer JR, Drake CG, Wollner I et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J. Clin. Oncol. 28, 3167-3175 (2010
92. Yang JC, Hughes M, Kammula U et al. Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J. Immunother. 30(8), 825-830 (2007 (Pubitemid 350295361)
93. Graber K. Companies waver in efforts to target transforming growth factor b in cancer. J. Natl Cancer Inst. 102, 1664-1667 (2009
94. Rescigno M, Avogadri F, Curigliano G. Challenges and prospects of immunotherapy as cancer treatment. Biochem. Biophys. Acta 1776(1), 108-123 (2007 (Pubitemid 47332077)
95. Hernandez JM, Bui MH, Han KR et al. Novel kidney cancer immunotherapy based in the granulocyte-macrophage colony-stimulating factor and carbonic anhydrase IX. Clin. Cancer Res. 9, 1906-1916 (2003 (Pubitemid 36554619)
96. Herbert N, Haferkamp A, Schmitz- Winnenthal, Zöller M. Concomitant tumor and autoantigen vaccination supports renal cell carcinoma rejection. J. Immunol. 185(2), 902-916 (2010
97. Finke JH, Rini B, Ireland J et al. Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients. Clin. Cancer Res. 14, 6674-6682 (2008
98. Hipp MM, Hilf N, Walter S et al. Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses. Blood 111, 5610-5620 (2008
99. Krusch M, Salih J, Schlicke M et al. The kinase inhibiitors sunitinib and sorafenib differentially affect NK cell antitumor reactivity in vitro. J. Immunol. 183, 8286-8294 (2009
100. Seliger B, Massa C, Rini B, Ko J, Finke J. Antitumor and immune-adjuvnat activities of protein-tyrosine kinase inhibitors. Trends Mol. Med. 16, 184-192 (2010
101. Roigas J. Lecture at the 3. Symposium. Presented at: Clinical and Experimental Research in Renal Cell Carcinoma. Jena, Germany, 29-30 October 2010.
102. Ablin RJ. Immunotherapy for prostatic cancer. Previous and prospective considerations. Oncology 31(3), 177-202 (1975
103. Märten A, Flieger D, Renoth S et al. 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(11-12), 637-644 (2002 (Pubitemid 35440517)
104. Su Z, Dannull J, Heiser A et al. Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells. Cancer Res. 63(9), 2127-2133 (2003 (Pubitemid 36538616)
105. Gitlitz BJ, Belldegrun AS, Zisman A et al. A pilot trial of tumor lysate-loaded dendritic cells for the treatment of metastatic renal cell carcinoma. J. Immunother. 26(5), 412-419 (2003 (Pubitemid 37128553)
106. Märten A, Renoth S, Heinicke T et al. 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(5), 483-494 (2003 (Pubitemid 36403540)
107. Arroyo JC, Gabilondo F, Llorente L et al. Immune response induced in vitro by CD16- and CD16+ monocyte-derived dendritic cells in patients with metastatic renal cell carcinoma treated with dendritic cell vaccines. J. Clin. Immunol. 24(1), 86-96 (2004 (Pubitemid 38375799)
108. Pandha HS, John RJ, Hutchinson J et al. Dendritic cell immunotherapy for urological cancers using cryopreserved allogeneic tumour lysate-pulsed cells: a Phase I/II study. BJU Int. 94(3), 412-418 (2004 (Pubitemid 39120190)
109. Wittig B, Märten A, Dorbic T et al. Therapeutic vaccination against metastatic carcinoma by expression-modulated and immunomodified autologous tumor cells: a first clinical Phase I/II trial. Hum. Gene Ther. 12(3), 267-278 (2001 (Pubitemid 32163898)
110. Tani K, Azuma M, Nakazaki Y et al. 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(4), 799-816 (2004). (Pubitemid 39272869)