Skip to main content

Prostate Cancer Vaccines Generated with the Disruptive RNActive® Technology Follow the Path Paved by Sipuleucel-T and Prostvac-VF

  • Chapter
  • First Online:
Cancer Immunotherapy Meets Oncology
  • 1861 Accesses

Abstract

Somewhat surprisingly, the first active cancer immunotherapy was approved with sipuleucel-T, an autologous cell therapy, in castrate-resistant prostate carcinoma rather than in melanoma, the test disease for many immunotherapies in the past. Sipuleucel-T is followed suit by other vaccines against prostate carcinoma that are now on advanced clinical development paths. Prostvac-VF is a viral vector vaccine using a heterologous prime–boost regimen to target PSA that has delivered promising phase IIb results. CV9103 is the first example in clinical testing of a vaccine engineered with the RNActive® technology. This technology uses a sequence modified mRNA molecule to ensure enhanced protein (antigen) expression and achieves good immune stimulation at the time by activation of TLR7. The nucleotide basis of CV9103 allowed inclusion of four different prostate-associated antigens in the vaccine. Safety and good immunogenicity of this novel approach were successfully demonstrated in a phase I/IIa study, and a further development of it is now in clinical phase IIb, proof-of-concept testing. These active immunotherapies can be combined successfully with other immunotherapies such as checkpoint inhibitors and may become pillars of anticancer immunotherapies.

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

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Literature

  • Arlen PM, Gulley JL, Todd N, Lieberman R, Steinberg SM, Morin S, Bastian A, Marte J, Tsang KY, Beetham P et al (2005) Antiandrogen, vaccine and combination therapy in patients with nonmetastatic hormone refractory prostate cancer. J Urol 174:539–546. doi:10.1158/1078-0432.CCR-07-0588

    Article  PubMed  CAS  Google Scholar 

  • Arlen PM, Gulley JL, Parker C, Skarupa L, Pazdur M, Panicali D, Beetham P, Tsang KY, Grosenbach DW, Feldman J et al (2006) A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer. Clin Cancer Res 12:1260–1269

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Arlen PM, Skarupa L, Pazdur M, Seetharam M, Tsang KY, Grosenbach DW, Feldman J, Poole DJ, Litzinger M, Steinberg SM et al (2007) Clinical safety of a viral vector based prostate cancer vaccine strategy. J Urol 178:1515–1520

    Article  PubMed  CAS  Google Scholar 

  • Banerjee AK (1980) 5′-terminal cap structure in eucaryotic messenger ribonucleic acids. Microbiol Rev 44:175–205

    PubMed Central  PubMed  CAS  Google Scholar 

  • Beer TM, Bernstein GT, Corman JM, Glode LM, Hall SJ, Poll WL, Schellhammer PF, Jones LA, Xu Y, Kylstra JW et al (2011) Randomized trial of autologous cellular immunotherapy with sipuleucel-T in androgen-dependent prostate cancer. Clin Cancer Res 17:4558–4567

    Article  PubMed  CAS  Google Scholar 

  • Bernstein DI, Cardin RD, Bravo FJ, Earwood J, Clark JR, Li Y, Mishra P, Li C, Nayak BP, Miller AT, et al (2012) Topical SMIP-7.7, a toll-like receptor 7 agonist, protects against genital herpes simplex virus-2 disease in the guinea pig model of genital herpes. Antivir Chem Chemother. doi:10.3851/IMP2499

  • Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Burnette BC, Liang H, Lee Y, Chlewicki L, Khodarev NN, Weichselbaum RR, Fu YX, Auh SL (2011) The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity. Cancer Res 71:2488–2496

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Butts C, Murray N, Maksymiuk A, Goss G, Marshall E, Soulieres D, Cormier Y, Ellis P, Price A, Sawhney R et al (2005) Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer. J Clin Oncol 23:6674–6681

    Article  PubMed  CAS  Google Scholar 

  • Butts CA, Socinski M, Mitchell P, Thatcher N, Havel L, Krzakowski MJ, Nawrocki S, Ciuleanu TE, Bosquée L, Perez JMT, et al (2013) START: a phase III study of L-BLP25 cancer immunotherapy for unresectable stage III non-small cell lung cancer. J Clin Oncol 31(suppl):abstr 7500

    Google Scholar 

  • de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L et al (2010) Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 376:1147–1154

    Article  PubMed  CAS  Google Scholar 

  • de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F et al (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364:1995–2005

    Article  PubMed Central  PubMed  Google Scholar 

  • Desmet CJ, Ishii KJ (2012) Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat Rev Immunol 12:479–491

    Article  PubMed  CAS  Google Scholar 

  • Diamond MS, Kinder M, Matsushita H, Mashayekhi M, Dunn GP, Archambault JM, Lee H, Arthur CD, White JM, Kalinke U et al (2011) Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med 208:1989–2003

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D, Bray F (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49:1374–1403

    Article  PubMed  CAS  Google Scholar 

  • Fotin-Mleczek M, Duchardt KM, Lorenz C, Pfeiffer R, Ojkic-Zrna S, Probst J, Kallen KJ (2011) Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity. J Immunother 34:1–15

    Article  PubMed  CAS  Google Scholar 

  • Fotin-Mleczek M, Zanzinger K, Heidenreich R, Lorenz C, Thess A, Duchardt KM, Kallen KJ (2012) Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect. J Gene Med 14:428–439

    Article  PubMed  CAS  Google Scholar 

  • Garnett CT, Schlom J, Hodge JW (2008) Combination of docetaxel and recombinant vaccine enhances T-cell responses and antitumor activity: effects of docetaxel on immune enhancement. Clin Cancer Res 14:3536–3544

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gulley JL, Drake CG (2011) Immunotherapy for prostate cancer: recent advances, lessons learned, and areas for further research. Clin Cancer Res 17:3884–3891

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gulley JL, Arlen PM, Madan RA, Tsang KY, Pazdur MP, Skarupa L, Jones JL, Poole DJ, Higgins JP, Hodge JW et al (2010) Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol Immunother 59:663–674

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gulley JL, Madan RA, Schlom J (2011) Impact of tumour volume on the potential efficacy of therapeutic vaccines. Curr Oncol 18:e150–e157

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gulley JL, Leitman SF, Dahut W, Schlom J (2012) Re: interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer. J Natl Cancer Inst 104:1106; author reply 1109–1112

    Article  PubMed  Google Scholar 

  • Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS et al (2013) Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 369:134–144

    Article  PubMed  CAS  Google Scholar 

  • Hartmann E, Wollenberg B, Rothenfusser S, Wagner M, Wellisch D, Mack B, Giese T, Gires O, Endres S, Hartmann G (2003) Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer. Cancer Res 63:6478–6487

    PubMed  CAS  Google Scholar 

  • Hartmann E, Graefe H, Hopert A, Pries R, Rothenfusser S, Poeck H, Mack B, Endres S, Hartmann G, Wollenberg B (2006) Analysis of plasmacytoid and myeloid dendritic cells in nasal epithelium. Clin Vaccine Immunol 13:1278–1286

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, Provost N, Frohlich MW (2009) Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer 115:3670–3679

    Article  PubMed  CAS  Google Scholar 

  • Hodge JW, Sabzevari H, Yafal AG, Gritz L, Lorenz MG, Schlom J (1999) A triad of costimulatory molecules synergize to amplify T-cell activation. Cancer Res 59:5800–5807

    PubMed  CAS  Google Scholar 

  • Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hoerr I, Obst R, Rammensee HG, Jung G (2000) In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies. Eur J Immunol 30:1–7

    Article  PubMed  CAS  Google Scholar 

  • Huber ML, Haynes L, Parker C, Iversen P (2012) Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer. J Natl Cancer Inst 104:273–279

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Iavarone C, Ramsauer K, Kubarenko AV, Debasitis JC, Leykin I, Weber AN, Siggs OM, Beutler B, Zhang P, Otten G et al (2011) A point mutation in the amino terminus of TLR7 abolishes signaling without affecting ligand binding. J Immunol 186:4213–4222

    Article  PubMed  CAS  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  • Julkunen I, Sareneva T, Pirhonen J, Ronni T, Melen K, Matikainen S (2001) Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression. Cytokine Growth Factor Rev 12:171–180

    Article  PubMed  CAS  Google Scholar 

  • Kallen K-J, Thess A (2014) A development that may evolve into a revolution in medicine: mRNA as the basis for novel, nucleotide-based vaccines and drugs. Ther Adv Vaccines 2:10–31. doi:10.1177/2051013613508729

    Article  PubMed Central  PubMed  Google Scholar 

  • Kallen KJ, Heidenreich R, Schnee M, Petsch B, Schlake T, Thess A, Baumhof P, Scheel B, Koch SD, Fotin-Mleczek M (2013) A novel, disruptive vaccination technology: Self-adjuvanted RNActive ((R)) vaccines. Hum Vaccin Immunother 9:2263–2276

    Article  PubMed Central  PubMed  Google Scholar 

  • Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB et al (2010a) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363:411–422

    Article  PubMed  CAS  Google Scholar 

  • Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M, Manson K, Panicali DL, Laus R, Schlom J et al (2010b) Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol 28:1099–1105

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kantoff PW, Higano CS, Small EJ, Whitmore JB, Frohlich MW, Schellhammer PF (2012) Re: interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer. J Natl Cancer Inst 104:1107–1109; author reply 1109–1112

    Article  PubMed  Google Scholar 

  • Ketterer T, von der Mülbe F, Reidel L, Mutzke T (2008) Method for purifying rna on a preparative scale by means of hplc. Patent WO2008077592

    Google Scholar 

  • Kreiter S, Selmi A, Diken M, Koslowski M, Britten CM, Huber C, Tureci O, Sahin U (2010) Intranodal vaccination with naked antigen-encoding RNA elicits potent prophylactic and therapeutic antitumoral immunity. Cancer Res 70:9031–9040

    Article  PubMed  CAS  Google Scholar 

  • Kreiter S, Diken M, Selmi A, Tureci O, Sahin U (2011) Tumor vaccination using messenger RNA: prospects of a future therapy. Curr Opin Immunol 23:399–406

    Article  PubMed  CAS  Google Scholar 

  • Kübler H, Maurer T, Stenzl A, Feyerabend S, Steiner U, Schostak M, Schultze-Seemann W, vom Dorp F, Pilla L, Viatali G et al (2011) Final analysis of a phase I/IIa study with CV9103, an intradermally administered prostate cancer immunotherapy based on self-adjuvanted mRNA. J Clin Oncol 29(suppl):abstr 4535

    Google Scholar 

  • Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T et al (2009) Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood 114:589–595

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Liang H, Deng L, Chmura S, Burnette B, Liadis N, Darga T, Beckett MA, Lingen MW, Witt M, Weichselbaum RR et al (2013) Radiation-induced equilibrium is a balance between tumor cell proliferation and T cell-mediated killing. J Immunol 190:5874–5881

    Article  PubMed  CAS  Google Scholar 

  • Lorenz C, Fotin-Mleczek M, Roth G, Becker C, Dam TC, Verdurmen WP, Brock R, Probst J, Schlake T (2011) Protein expression from exogenous mRNA: uptake by receptor-mediated endocytosis and trafficking via the lysosomal pathway. RNA Biol 8:627–636

    Article  PubMed  CAS  Google Scholar 

  • Madan RA, Gulley JL, Schlom J, Steinberg SM, Liewehr DJ, Dahut WL, Arlen PM (2008) Analysis of overall survival in patients with nonmetastatic castration-resistant prostate cancer treated with vaccine, nilutamide, and combination therapy. Clin Cancer Res 14:4526–4531

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Madan RA, Bilusic M, Heery C, Schlom J, Gulley JL (2012a) Clinical evaluation of TRICOM vector therapeutic cancer vaccines. Semin Oncol 39:296–304

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Madan RA, Mohebtash M, Arlen PM, Vergati M, Rauckhorst M, Steinberg SM, Tsang KY, Poole DJ, Parnes HL, Wright JJ et al (2012b) Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. Lancet Oncol 13:501–508

    Article  PubMed  CAS  Google Scholar 

  • Mbow ML, De Gregorio E, Valiante NM, Rappuoli R (2010) New adjuvants for human vaccines. Curr Opin Immunol 22:411–416

    Article  PubMed  CAS  Google Scholar 

  • McNeel DG, Dunphy EJ, Davies JG, Frye TP, Johnson LE, Staab MJ, Horvath DL, Straus J, Alberti D, Marnocha R et al (2009) Safety and immunological efficacy of a DNA vaccine encoding prostatic acid phosphatase in patients with stage D0 prostate cancer. J Clin Oncol 27:4047–4054

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Naik SH, Metcalf D, van Nieuwenhuijze A, Wicks I, Wu L, O’Keeffe M, Shortman K (2006) Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nat Immunol 7:663–671

    Article  PubMed  CAS  Google Scholar 

  • North SA, Graham K, Bodnar D, Venner P (2006) A pilot study of the liposomal MUC1 vaccine BLP25 in prostate specific antigen failures after radical prostatectomy. J Urol 176:91–95

    Article  PubMed  CAS  Google Scholar 

  • Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fossa SD, Chodacki A, Wiechno P, Logue J, Seke M et al (2013) Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 369:213–223

    Article  PubMed  CAS  Google Scholar 

  • Pascolo S (2004) Messenger RNA-based vaccines. Expert Opin Biol Ther 4:1285–1294

    Article  PubMed  CAS  Google Scholar 

  • Pascolo S (2006) Vaccination with messenger RNA. Methods Mol Med 127:23–40

    PubMed  CAS  Google Scholar 

  • Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M et al (2004) Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351:1513–1520

    Article  PubMed  CAS  Google Scholar 

  • Petsch B, Schnee M, Vogel AB, Lange E, Hoffmann B, Voss D, Schlake T, Thess A, Kallen KJ, Stitz L et al (2012) Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat Biotechnol 30:1210–1216

    Article  PubMed  CAS  Google Scholar 

  • Reits EA, Hodge JW, Herberts CA, Groothuis TA, Chakraborty M, Wansley EK, Camphausen K, Luiten RM, de Ru AH, Neijssen J et al (2006) Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med 203:1259–1271

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Rittig SM, Haentschel M, Weimer KJ, Heine A, Muller MR, Brugger W, Horger MS, Maksimovic O, Stenzl A, Hoerr I et al (2011) Intradermal vaccinations with RNA coding for TAA generate CD8+ and CD4+ immune responses and induce clinical benefit in vaccinated patients. Mol Ther 19:990–999

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ et al (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364:2517–2526

    Article  PubMed  CAS  Google Scholar 

  • Russo C, Cornella-Taracido I, Galli-Stampino L, Jain R, Harrington E, Isome Y, Tavarini S, Sammicheli C, Nuti S, Mbow ML et al (2011) Small molecule Toll-like receptor 7 agonists localize to the MHC class II loading compartment of human plasmacytoid dendritic cells. Blood 117:5683–5691

    Article  PubMed  CAS  Google Scholar 

  • Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S et al (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138–148

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Scheel B, Teufel R, Probst J, Carralot JP, Geginat J, Radsak M, Jarrossay D, Wagner H, Jung G, Rammensee HG et al (2005) Toll-like receptor-dependent activation of several human blood cell types by protamine-condensed mRNA. Eur J Immunol 35:1557–1566

    Article  PubMed  CAS  Google Scholar 

  • Schellhammer PF, Chodak G, Whitmore JB, Sims R, Frohlich MW, Kantoff PW (2013) Lower baseline prostate-specific antigen is associated with a greater overall survival benefit from sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial. Urology 81:1297–1302

    Article  PubMed  Google Scholar 

  • Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R et al (2008) Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 26:1148–1159

    Article  PubMed  Google Scholar 

  • Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND et al (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367:1187–1197

    Article  PubMed  CAS  Google Scholar 

  • Schlake T, Thess A, Fotin-Mleczek M, Kallen KJ (2012) Developing mRNA-vaccine technologies. RNA Biol 9:1319–1330

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Sebastian M, von Boehmer L, Zippelius A, Mayer F, Reck M, Atanackovic D, Thomas M, Schneller F, Stoehlmacher J, Goekkurt E et al (2011) Messenger RNA vaccination in NSCLC: Findings from a phase I/IIa clinical trial. J Clin Oncol 29(suppl):abstr 2584

    Google Scholar 

  • Sebastian M, von Boehmer L, Zippelius A, Mayer F, Reck M, Atanackovic D, Thomas M, Schneller F, Stoehlmacher-William J, Goekkurt E et al (2012) Messenger RNA vaccination and B-cell responses in NSCLC patients. J Clin Oncol 30(suppl):abstr 2573

    Google Scholar 

  • Sheikh NA, Petrylak D, Kantoff PW, Dela Rosa C, Stewart FP, Kuan LY, Whitmore JB, Trager JB, Poehlein CH, Frohlich MW et al (2013) Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer. Cancer Immunol Immunother 62:137–147

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM (2006) Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 24:3089–3094

    Article  PubMed  CAS  Google Scholar 

  • Spranger S, Javorovic M, Burdek M, Wilde S, Mosetter B, Tippmer S, Bigalke I, Geiger C, Schendel DJ, Frankenberger B (2010) Generation of Th1-polarizing dendritic cells using the TLR7/8 agonist CL075. J Immunol 185:738–747

    Article  PubMed  CAS  Google Scholar 

  • Spranger S, Frankenberger B, Schendel DJ (2012) NOD/scid IL-2Rg(null) mice: a preclinical model system to evaluate human dendritic cell-based vaccine strategies in vivo. J Transl Med 10:30

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Stein WD, Gulley JL, Schlom J, Madan RA, Dahut W, Figg WD, Ning YM, Arlen PM, Price D, Bates SE et al (2011) Tumor regression and growth rates determined in five intramural NCI prostate cancer trials: the growth rate constant as an indicator of therapeutic efficacy. Clin Cancer Res 17:907–917

    Article  PubMed  CAS  Google Scholar 

  • Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I et al (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502–1512

    Article  PubMed  CAS  Google Scholar 

  • Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Van Lint S, Goyvaerts C, Maenhout S, Goethals L, Disy A, Benteyn D, Pen J, Bonehill A, Heirman C, Breckpot K et al (2012) Preclinical evaluation of TriMix and antigen mRNA-based antitumor therapy. Cancer Res 72:1661–1671

    Article  PubMed  CAS  Google Scholar 

  • Van Nuffel AM, Wilgenhof S, Thielemans K, Bonehill A (2012) Overcoming HLA restriction in clinical trials: Immune monitoring of mRNA-loaded DC therapy. Oncoimmunology 1:1392–1394

    Article  PubMed Central  PubMed  Google Scholar 

  • Walsh KB, Teijaro JR, Zuniga EI, Welch MJ, Fremgen DM, Blackburn SD, von Tiehl KF, Wherry EJ, Flavell RA, Oldstone MB (2012) Toll-like receptor 7 is required for effective adaptive immune responses that prevent persistent virus infection. Cell Host Microbe 11:643–653

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Walter S, Weinschenk T, Stenzl A, Zdrojowy R, Pluzanska A, Szczylik C, Staehler M, Brugger W, Dietrich PY, Mendrzyk R et al (2012) Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med 18:1254–1261

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Weide B, Pascolo S, Scheel B, Derhovanessian E, Pflugfelder A, Eigentler TK, Pawelec G, Hoerr I, Rammensee HG, Garbe C (2009) Direct injection of protamine-protected mRNA: results of a phase 1/2 vaccination trial in metastatic melanoma patients. J Immunother 32:498–507

    Article  PubMed  CAS  Google Scholar 

  • Wickens M (1990) How the messenger got its tail: addition of poly(A) in the nucleus. Trends Biochem Sci 15:277–281

    Article  PubMed  CAS  Google Scholar 

  • Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K et al (2013) Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 369:122–133

    Article  PubMed  CAS  Google Scholar 

  • Wollenberg A, Wagner M, Gunther S, Towarowski A, Tuma E, Moderer M, Rothenfusser S, Wetzel S, Endres S, Hartmann G (2002) Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. J Invest Dermatol 119:1096–1102

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Karl-Josef Kallen MD, PhD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Kallen, KJ. (2014). Prostate Cancer Vaccines Generated with the Disruptive RNActive® Technology Follow the Path Paved by Sipuleucel-T and Prostvac-VF. In: Britten, C., Kreiter, S., Diken, M., Rammensee, HG. (eds) Cancer Immunotherapy Meets Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-05104-8_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-05104-8_15

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-05103-1

  • Online ISBN: 978-3-319-05104-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics