Abstract
Although new treatment options for patients with advanced renal cell cancer (RCC) have been developed within recent years, vaccination is still a promising emerging treatment option. An increasing number of tumor-associated antigens (TAA) available for RCC are currently used and analyzed for their efficacy for antigen-specific vaccine strategies. Recently, antigen-specific vaccination with dendritic cells in patients with metastatic RCC was shown to induce cytotoxic T cell response associated with objective clinical responses in some of the patients. Furthermore, current studies focus on the development of more effective vaccine regimes, such as the application of polyvalent, HLA-independent RNA coding for multiple TAA and adjuvants. First results demonstrate promising clinical and immunological efficacy. The efficacy of antigen-specific vaccination might be improved by a combination of tyrosine kinase inhibitors, since sunitinib was shown to promote T cell induction following vaccination in a mouse model and elimination of regulatory T cells.
Similar content being viewed by others
References
Antonia SJ, Seigne J, Diaz J, Muro-Cacho C, Extermann M, Farmelo MJ, Friberg M, Alsarraj M, Mahany JJ, Pow-Sang J, Cantor A, Janssen W (2002) 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 167:1995–2000
Atzpodien J, Kirchner H, Jonas U, Bergmann L, Schott H, Heynemann H, Fornara P, Loening SA, Roigas J, Müller SC, Bodenstein H, Pomer S, Metzner B, Rebmann U, Oberneder R, Siebels M, Wandert T, Puchberger M, Reitz T, The German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN) (2004) Prospectively randomized trial: interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma. J Clin Oncol 22:1188–1194
Avigan DE, Vasir B, George DJ, Oh WK, Atkins MB, McDermott DF, Kantoff PW, Figlin RA, Vasconcelles MJ, Xu Y, Kufe D, Bukowski RM (2007) 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 30:749–761
Berntsen A, Trepiakas R, Wenandy L, Geertsen PF, thor Straten P, Andersen MH, Pedersen AE, Claesson MH, Lorentzen T, Johansen JS, Svane IM (2008) Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial. J Immunother 31:771–780
Bleumer I, Tiemessen DM, Oosterwijk-Wakka JC, Völler MC, De Weijer K, Mulders PF, Oosterwijk E (2007) Preliminary analysis of patients with progressive renal cell carcinoma vaccinated with CA9-peptide-pulsed mature dendritic cells. J Immunother 30:116–122
Boss CN, Grünebach F, Brauer K, Häntschel M, Mirakaj V, Weinschenk T, Stevanovic S, Rammensee HG, Brossart P (2007) Identification and characterization of T cell epitopes deduced from RGS5, a novel broadly expressed tumor antigen. Clin Cancer Res 13:3347–3355
Buechler C, Ritter M, Duong CQ, Orso E, Kapinsky M, Schmitz G (2001) Adipophilin is a sensitive marker for lipid loading in human blood monocytes. Biochim Biophys Acta 1532:97–104
Byun SS, Yeo WG, Lee SE, Lee E (2007) Expression of survivin in renal cell carcinomas: association with pathologic features and clinical outcome. Urology 69:34–37
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 24:1169–1177
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 10:942–949
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 115:3623–3633
Dikov MM, Oyama T, Cheng P, Takahashi T, Takahashi K, Sepetavec T, Edwards B, Adachi Y, Nadaf S, Daniel T, Gabrilovich DI, Carbone DP (2001) Vascular endothelial growth factor effects on nuclear factor-kappaB activation in hematopoietic progenitor cells. Cancer Res 61:2015–2021
Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM (2007) TARGET Study Group: sorafenib in advanced clear-cell renal cell carcinoma. N Engl J Med 356:125–134
Finke JH, Rini B, Ireland J, Rayman P, Richmond A, Golshayan A, Wood L, Elson P, Garcia J, Dreicer R, Bukowski R (2008) Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients. Clin Cancer Res 14:6674–6682
Gabrilovich D, Ishida T, Oyama T, Ran S, Kravtsov V, Nadaf S, Carbone DP (1998) Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92:4150–4166
Glaspy JA (2002) Therapeutic options in the management of renal cell carcinoma. Semin Oncol 29:41–46
Gouttefangeas C, Stenzl A, Stevanović S, Rammensee HG (2007) Immunotherapy of renal cell carcinoma. Cancer Immunol Immunother 56:117–128
Heid HW, Moll R, Schwetlick I, Rackwitz HR, Keenan TW (1998) Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases. Cell Tissue Res 294:309–321
Hess PR, Boczkowski D, Nair SK, Snyder D, Gilboa E (2006) Vaccination with mRNAs encoding tumor-associated antigens and granulocyte-macrophage colony-stimulating factor efficiently primes CTL responses, but is insufficient to overcome tolerance to a model tumor/self antigen. Cancer Immunol Immunother 55:672–683
Hipp MM, Hilf N, Walter S, Werth D, Brauer KM, Radsak MP, Weinschenk T, Singh-Jasuja H, Brossart P (2008) Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses. Blood 111:5610–5620
Höltl L, Rieser C, Papesh C, Ramoner R, Herold M, Klocker H, Radmayr C, Stenzl A, Bartsch G, Thurnher M (1999) Cellular and humoral immune responses in patients with metastatic renal cell carcinoma after vaccination with antigen pulsed dendritic cells. J Urol 161:777–782
Höltl 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 8:3369–3376
Höltl L, Ramoner R, Zelle-Rieser C, Gander H, Putz T, Papesh C, Nussbaumer W, Falkensammer C, Bartsch G, Thurnher M (2004) Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma with or without cyclophosphamide. Cancer Immunol Immunother 54:663–670
Jerome KR, Domenech N, Finn OJ (1993) Tumor-specific cytotoxic T cell clones from patients with breast and pancreatic adenocarcinoma recognize EBV-immortalized B cells transfected with polymorphic epithelial mucin complementary DNA. J Immunol 151:1654–1662
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 363:594–599
Jonasch E, Wood C, Tamboli P, Pagliaro LC, Tu SM, Kim J, Srivastava P, Perez C, Isakov L, Tannir N (2008) Vaccination of metastatic renal cell carcinoma patients with autologous tumour-derived vitespen vaccine: clinical findings. Br J Cancer 98:1336–1341
Motzer RJ, Bander NH, Nanus DM (1996) Renal cell carcinoma. N Engl J Med 335:865–875
Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA (2007) Sunitinib versus interferon alfa in metastatic renal cell carcinoma. N Engl J Med 356:115–124
Ohm JE, Shurin MR, Esche C, Lotze MT, Carbone DP, Gabrilovich DI (1999) Effect of vascular endothelial growth factor and FLT3 ligand on dendritic cell generation in vivo. J Immunol 163:3260–3268
Oka H, Chatani Y, Hoshino R, Ogawa O, Kakehi Y, Terachi T, Okada Y, Kawaichi M, Kohno M, Yoshida O (1995) Constitutive activation of mitogen-activated protein (MAP) kinases in human renal cell carcinoma. Cancer Res 55:4182–4187
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 25:500–508
Rae FK, Stephenson SA, Nicol DL, Clements JA (2000) Novel association of a diverse range of genes with renal cell carcinoma as identified by differential display. Int J Cancer 88:726–732
Rosenberg SA, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE (1994) Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 271:1–907
Schag K, Schmidt SM, Müller MR, Weinschenk T, Appel S, Weck MM, Grünebach 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 10:3658–3666
Schmidt SM, Schag K, Müller MR, Weinschenk T, Appel S, Schoor O, Weck MM, Grünebach 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 64:1164–1170
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 63:2127–2133
Suekane S, Nishitani M, Noguchi M, Komohara Y, Kokubu T, Naitoh M, Honma S, Yamada A, Itoh K, Matsuoka K, Kanayama H (2007) Phase I trial of personalized peptide vaccination for cytokine-refractory metastatic renal cell carcinoma patients. Cancer Sci 98:1965–1968
Takahashi T, Kuniyasu Y, Toda M, Sakaguchi N, Itoh M, Iwata M, Shimizu J, Sakaguchi S (1998) Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol 10:1969–1980
Uemura H, Nakagawa Y, Yoshida K, Saga S, Yoshikawa K, Hirao Y, Oosterwijk E (1999) MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas. Br J Cancer 81:741–746
Uemura H, Fujimoto K, Tanaka M, Yoshikawa M, Hirao Y, Uejima S, Yoshikawa K, Itoh K (2006) 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 12:1768–1775
Villegas G, Lange-Sperandio B, Tufro A (2005) Autocrine and paracrine functions of vascular endothelial growth factor (VEGF) in renal tubular epithelial cells. Kidney Int 67:449–457
Vosper H, Patel L, Graham TL, Khoudoli GA, Hill A, Macphee CH, Pinto I, Smith SA, Suckling KE, Wolf CR, Palmer CN (2001) The peroxisome proliferator-activated receptor delta promotes lipid accumulation in human macrophages. J Biol Chem 276:44258–44265
Weide B, Carralot JP, Reese A, Scheel B, Eigentler TK, Hoerr I, Rammensee HG, Garbe C, Pascolo S (2008) Results of the first phase I/II clinical vaccination trial with direct injection of mRNA. J Immunother 31:180–188
Weinschenk T, Gouttefangeas C, Schirle M, Obermayr F, Walter S, Schoor O, Kurek R, Loeser W, Bichler KH, Wernet D, Stevanović S, Rammensee HG (2002) Integrated functional genomics approach for the design of patient-individual antitumor vaccines. Cancer Res 62:5818–5827
Wierecky J, Müller MR, Wirths S, Halder-Oehler E, Dörfel D, Schmidt SM, Häntschel M, Brugger W, Schröder S, Horger MS, Kanz L, Brossart P (2006) Immunologic and clinical responses after vaccinations with peptide-pulsed dendritic cells in metastatic renal cancer patients. Cancer Res 66:5910–5918
Wirth MP (1993) Immunotherapy for metastatic renal cell carcinoma. Urol Clin North Am 20:283–295
Wood C, Srivastava P, Bukowski R, Lacombe L, Gorelov AI, Gorelov S, Mulders P, Zielinski H, Hoos A, Teofilovici F, Isakov L, Flanigan R, Figlin R, Gupta R, Escudier B, C-100–12 RCC Study Group (2008) An adjuvant autologous therapeutic vaccine (HSPPC-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
Yang CJ, Beck KE, Blansfield JA, Tran KQ, Lowy I, Rosenberg SA (2005) Tumor regression in patients with metastatic renal cancer treated with a monoclonal antibody to CTLA4 (MDX-010) ASCO meeting abstract. J clin oncol 23 (Suppl 16)
Zhou X, Jun DY, 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 65:1079–1088
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Asemissen, A.M., Brossart, P. Vaccination strategies in patients with renal cell carcinoma. Cancer Immunol Immunother 58, 1169–1174 (2009). https://doi.org/10.1007/s00262-009-0706-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00262-009-0706-7