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Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer


In newly diagnosed metastatic hormone-naive prostate cancer (mPC), telomerase-based immunotherapy with the novel hTERT peptide vaccine UV1 can induce immune responses with potential clinical benefit. This phase I dose escalation study of UV1 evaluated safety, immune response, effects on prostate-specific antigen (PSA) levels, and preliminary clinical outcome. Twenty-two patients with newly diagnosed metastatic hormone-naïve PC (mPC) were enrolled; all had started androgen deprivation therapy and had no visceral metastases. Bone metastases were present in 17 (77%) patients and 16 (73%) patients had affected lymph nodes. Three dose levels of UV1 were given as intradermal injections combined with GM-CSF (Leukine®). Twenty-one patients in the intention-to-treat population (95%) received conformal radiotherapy. Adverse events reported were predominantly grade 1, most frequently injection site pruritus (86.4%). Serious adverse events considered possibly related to UV1 and/or GM-CSF included anaphylactic reaction in two patients and thrombocytopenia in one patient. Immune responses against UV1 peptides were confirmed in 18/21 evaluable patients (85.7%), PSA declined to <0.5 ng/mL in 14 (64%) patients and in ten patients (45%) no evidence of persisting tumour was seen on MRI in the prostatic gland. At the end of the nine-month reporting period for the study, 17 patients had clinically stable disease. Treatment with UV1 and GM-CSF gave few adverse events and induced specific immune responses in a large proportion of patients unselected for HLA type. The intermediate dose of 0.3 mg UV1 resulted in the highest proportion of, and most rapid UV1-specific immune responses with an acceptable safety profile. These results warrant further clinical studies in mPC.

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Androgen deprivation therapy


Good clinical practice


Human telomerase reverse transcriptase


Prostate cancer clinical trials working group


Progressive disease


Prostate-specific antigen


Stable disease


Stimulation index


  1. 1.

    Lilleby W, Hernes E, Wæhre H, Raabe N, Fosså SD (2006) Treatment of hormone-resistant prostate cancer. Tidsskr Nor Laegeforen 126:2798–2801

    PubMed  Google Scholar 

  2. 2.

    Lilleby W, Narang A, Tafjord G, Vlatkovic L, Russnes KM, Stensvold A, Hole KH, Tran PT, Eilertsen K (2015) Favorable outcomes in locally advanced and node positive prostate cancer patients treated with combined pelvic IMRT and androgen deprivation therapy. Radiat Oncol 10:232–237. doi:10.1186/s13014-015-0540-3

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Kyte JA (2009) Cancer vaccination with telomerase peptide GV1001. Expert Opin Investig Drugs 18:687–694

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Su Z, Dannull J, Yang BK et al (2005) Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer. J Immunol 174:3798–3807

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Zanetti M (2017) A second chance for telomerase reverse transcriptase in anticancer immunotherapy. Nat Rev Clin Oncol 14:115–128. doi:10.1038/nrclinonc.2016.67

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Li J, Li H, Liu J, Feng B, Feng M, Lv B, Cheng S, Yang X (2016) The clinical implications of human telomerase reverse transcriptase expression in grade and prognosis of gliomas: a systematic review and meta-analysis. Mol Neurobiol 53:2887–2893. doi:10.1007/s12035-015-9170-x

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Shin JS, Foo T, Hong A, Zhang M, Lum T, Solomon MJ, Lee CS (2012) Telomerase expression as a predictive marker of radiotherapy response in rectal cancer. Pathology 44:209–215. doi:10.1097/PAT.0b013e3283511cd5

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Inderberg-Suso EM, Trachsel S, Lislerud K, Rasmussen AM, Gaudernack G (2012) Widespread CD4+ T cell reactivity to novel hTERT epitopes following vaccination of cancer patients with a single hTERT peptide GV1001. Oncoimmunology 1:670–686. doi:10.4161/onci.20426

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. doi:10.1016/j.ejca.2008.10.026

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Scher HI, Halabi S, Tannock T et al (2008) Design and endpoints of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone. J Clin Oncol 26:1148–1159

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Kyte JA, Mu L, Aamdal S et al (2006) Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA. Cancer Gene Ther 13:905–918

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Kyte JA, Kvalheim G, Aamdal S, Saeboe-Larssen S, Gaudernack G (2005) Preclinical full-scale evaluation of dendritic cells transfected with autologous tumor-mRNA for melanoma vaccination. Cancer Gene Ther 12:579–591

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Suso EM, Dueland S, Rasmussen AM, Vetrhus T, Aamdal S, Kvalheim G, Gaudernack G (2011) hTERT mRNA dendritic cell vaccination: complete response in a pancreatic cancer patient associated with response against several hTERT epitopes. Cancer Immunol Immunother 60:809–818

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Charo J, Perez C, Buschow C, Jukica A, Czeh M, Blankenstein T (2011) Visualizing the dynamic of adoptively transferred T cells during the rejection of large established tumors. Eur J Immunol 41:3187–3197

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    van Poelgeest MI, Welters MJ, Vermeij R et al (2016) Vaccination against oncoproteins of HPV16 for noninvasive vulvar/vaginal lesions: lesion clearance is related to the strength of the T cell response. Clin Cancer Res 22:2342–2350. doi:10.1158/1078-0432.CCR-15-2594

    Article  PubMed  Google Scholar 

  16. 16.

    Brunsvig PF, Aamdal S, Gjertsen MK et al (2006) Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer. Cancer Immunol Immunother 55:1553–1564

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Kwon ED, Drake CG, Scher HI et al (2014) Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 15:700–712. doi:10.1016/S1470-2045(14)70189-5

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    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. doi:10.1016/j.urology.2013.01.061

    Article  PubMed  Google Scholar 

  19. 19.

    Nemunaitis J, Susan N, Rabinowe ND et al (1991) Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. Accessed 20 Feb 2017

  20. 20.

    Heidenreich A (2015) New developments in the management of prostate cancer. Oncol Res Treat 38:628. doi:10.1159/000442269

    Article  PubMed  Google Scholar 

  21. 21.

    Narang AK, Gergis C, Robertson SP et al (2016) Very high-risk localized prostate cancer: outcomes following definitive radiation. Int J Radiat Oncol Biol Phys 94:254–262. doi:10.1016/j.ijrobp.2015.10.056

    Article  PubMed  Google Scholar 

  22. 22.

    Mercader M, Bodner BK, Moser MT et al. (2001) T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer. Proc Natl Acad Sci 98:14565–14570. doi:10.1073/pnas.251140998

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Wolchok JD, Hoos A, O’Day S et al (2009) Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Can Res 15:7412–7420

    CAS  Article  Google Scholar 

  24. 24.

    Sweeney CJ, Chen YH, Carducci M et al (2015) Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 373:737–746. doi:10.1056/NEJMoa1503747

  25. 25.

    Brunsvig PF, Kyte JA, Kersten C, Sundstrom S, Moller M, Nyakas M, Hansen GL, Gaudernack G, Aamdal S (2011) Telomerase peptide vaccination in NSCLC: a phase II trial in stage III patients vaccinated after chemoradiotherapy and an 8-year update on a phase I/II trial. Clin Can Res 17:6847–6857

    CAS  Article  Google Scholar 

  26. 26.

    Harris TJ, Hipkiss EL, Borzillary S et al (2008) Radiotherapy augments the immune response to prostate cancer in a time-dependent manner. Prostate 68:1319–1329. doi:10.1002/pros.20794

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Nesslinger NJ, Sahota RA, Stone B et al (2007) Standard treatments induce antigen-specific immune responses in prostate cancer. Clin Cancer Res 13:1493–1502

    CAS  Article  PubMed  Google Scholar 

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We thank all the patients for their participation in the study. Furthermore, we also appreciate the excellent administrative assistance of Signe Fretland and Dovile Kuliesiute and thank Grete Berntsen for excellent technical assistance with immunomonitoring. We thank Ingunn Westgaard for critical reading of the manuscript.


This study was supported by The Norwegian Research Council (FORNY program), Innovation Norway AS, Ultimovacs AS.

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Corresponding author

Correspondence to Wolfgang Lilleby.

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Conflict of interest

Gustav Gaudernack is an employee and a shareholder in Ultimovacs AS. Gustav Gaudernack and Else Marit Inderberg are inventors on the UV1 vaccine patent. All other authors declare that no conflict of interest exists.

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Lilleby, W., Gaudernack, G., Brunsvig, P.F. et al. Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer. Cancer Immunol Immunother 66, 891–901 (2017).

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  • Prostate cancer
  • hTERT
  • Cancer vaccine
  • Immune response