Immunologic Research

, Volume 59, Issue 1–3, pp 229–235 | Cite as

Vaccine immunotherapy for prostate cancer: from mice to men

  • David M. Lubaroff
  • Daniel Vaena
  • James A. Brown
  • Pamela Zehr
  • Karen C. Griffith
  • Erica Brown
  • Julie Eastman
  • Kenneth Nepple
  • Ambika Kattula
  • Richard D. Williams
IMMUNOLOGY AT THE UNIVERSITY OF IOWA

Abstract

Preclinical studies demonstrated the ability of an adenovirus/PSA (Ad/PSA) vaccine to induce strong anti-PSA immune responses, and these responses were capable of destroying prostate-specific antigen (PSA)-secreting mouse prostate tumors. A series of preclinical studies have demonstrated the superiority of the Ad/PSA vaccine to other PSA vaccines for the induction of anti-PSA immune responses, the ability of Ad/PSA vaccination combined with cytokine gene therapy and the TLR9 agonist CpG to enhance the anti-prostate tumor immunotherapy, and the reduction of negative regulatory elements when the vaccine was combined with 5-fluoruracil administration. A phase I clinical trial of the Ad/PSA vaccine in men with metastatic castrate-resistant prostate cancer demonstrated the safety of the vaccine even at the highest single dose permitted by the FDA. Currently, a phase II trial of the Ad/PSA vaccine is underway treating patients in two protocols. Thus far 81 patients have been enrolled and vaccinated. Early results from the patients evaluated to date demonstrated the induction of anti-PSA T cell responses, and the majority of patients evaluated at this time had demonstrated an increase in PSA doubling times.

Keywords

Prostate cancer Vaccine Immunotherapy Clinical trials 

References

  1. 1.
    Siegel R, et al. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.CrossRefPubMedGoogle Scholar
  2. 2.
    Heidenreich A, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol. 2011;59(1):61–71.CrossRefPubMedGoogle Scholar
  3. 3.
    Thompson I, et al. Guideline for the management of clinically localized prostate cancer: 2007 update. J Urol. 2007;177(6):2106–31.CrossRefPubMedGoogle Scholar
  4. 4.
    Gaztanaga M, Crook J. Androgen deprivation therapy: minimizing exposure and mitigating side effects. J Natl Comp Cancer Netw. 2012;10(9):1088–95 quiz 1088, 1096.Google Scholar
  5. 5.
    de Bono JS, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376(9747):1147–54.CrossRefPubMedGoogle Scholar
  6. 6.
    Tannock IF, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502–12.CrossRefPubMedGoogle Scholar
  7. 7.
    Attard G, et al. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol. 2009;27(23):3742–8.PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Nadal R, Taplin ME, Bellmunt J. Enzalutamide for the treatment of prostate cancer: results and implications of the AFFIRM trial. Future Oncol. 2014;10(3):351–62.CrossRefPubMedGoogle Scholar
  9. 9.
    Lubaroff DM. Prostate cancer vaccines in clinical trials. Expert Rev Vaccines. 2012;11(7):857–68.CrossRefPubMedGoogle Scholar
  10. 10.
    Buckwalter MR, Srivastava PK. “It is the antigen(s), stupid” and other lessons from over a decade of vaccitherapy of human cancer. Semin Immunol. 2008;20(5):296–300.CrossRefPubMedGoogle Scholar
  11. 11.
    Elzey BD, et al. Immunization with type 5 adenovirus recombinant for a tumor antigen in combination with recombinant canary pox virus (ALVAC) cytokine gene delivery induces destruction of established prostate tumors. Int J Cancer. 2001;94(6):842–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Karan D, Krieg AM, Lubaroff DM. Paradoxical enhancement of CD8 T cell-dependent anti-tumor protection despite reduced CD8 T cell responses with addition of a TLR9 agonist to a tumor vaccine. Int J Cancer. 2007;121(7):1520–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Lubaroff DM, et al. Decreased cytotoxic T cell activity generated by co-administration of PSA vaccine and CpG ODN is associated with increased tumor protection in a mouse model of prostate cancer. Vaccine. 2006;24(35–36):6155–62.CrossRefPubMedGoogle Scholar
  14. 14.
    Geary SM, et al. Tumor immunotherapy using adenovirus vaccines in combination with intratumoral doses of CpG ODN. Cancer Immunol Immunother CII. 2011;60(9):1309–17.CrossRefPubMedGoogle Scholar
  15. 15.
    Madan RA, et al. Clinical evaluation of TRICOM vector therapeutic cancer vaccines. Semin Oncol. 2012;39(3):296–304.PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Kuriyama S, Tominaga K, Kikukawa M, Nakatani T, Tsujinoue H, Yamazaki M, Nagao S, Toyokawa Y, Mitoro A, Fukui H. Inhibitory effects of human sera on adenovirus-mediated gene transfer into rat liver. Anticancer Res. 1998;18:2345.PubMedGoogle Scholar
  17. 17.
    Siemens DR, et al. Cutting edge: restoration of the ability to generate CTL in mice immune to adenovirus by delivery of virus in a collagen-based matrix. J Immunol. 2001;166(2):731–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Joshi VB, Geary SM, Salem AK. Biodegradable particles as vaccine antigen delivery systems for stimulating cellular immune responses. Hum Vaccin Immunother. 2013;9(12):2584–90.PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Lubaroff DM, et al. Clinical protocol: phase I study of an adenovirus/prostate-specific antigen vaccine in men with metastatic prostate cancer. Hum Gene Ther. 2006;17(2):220–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Lubaroff DM, et al. Phase I clinical trial of an adenovirus/prostate-specific antigen vaccine for prostate cancer: safety and immunologic results. Clin Cancer Res. 2009;15(23):7375–80.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Halabi S, et al. Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer. J Clin Oncol. 2003;21(7):1232–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Drake CG, et al. Androgen ablation mitigates tolerance to a prostate/prostate cancer-restricted antigen. Cancer Cell. 2005;7(3):239–49.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Mercader M, et al. T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer. Proc Natl Acad Sci USA. 2001;98(25):14565–70.PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Roden AC, et al. Augmentation of T cell levels and responses induced by androgen deprivation. J Immunol. 2004;173(10):6098–108.CrossRefPubMedGoogle Scholar
  25. 25.
    Sutherland JS, et al. Activation of thymic regeneration in mice and humans following androgen blockade. J Immunol. 2005;175(4):2741–53.CrossRefPubMedGoogle Scholar
  26. 26.
    Bronte V, Mocellin S. Suppressive influences in the immune response to cancer. J Immunother. 2009;32(1):1–11.CrossRefPubMedGoogle Scholar
  27. 27.
    Geary SM, et al. The combination of a low-dose chemotherapeutic agent, 5-fluorouracil, and an adenoviral tumor vaccine has a synergistic benefit on survival in a tumor model system. PLoS One. 2013;8(6):e67904.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • David M. Lubaroff
    • 1
    • 2
    • 4
  • Daniel Vaena
    • 1
    • 3
    • 4
    • 5
  • James A. Brown
    • 1
    • 4
    • 5
  • Pamela Zehr
    • 4
  • Karen C. Griffith
    • 5
  • Erica Brown
    • 1
  • Julie Eastman
    • 5
  • Kenneth Nepple
    • 1
    • 4
    • 5
  • Ambika Kattula
    • 1
  • Richard D. Williams
    • 1
    • 4
  1. 1.Department of UrologyUniversity of IowaIowa CityUSA
  2. 2.Department of MicrobiologyUniversity of IowaIowa CityUSA
  3. 3.Department of Internal MedicineUniversity of IowaIowa CityUSA
  4. 4.Holden Comprehensive Cancer CenterUniversity of IowaIowa CityUSA
  5. 5.Department of Veterans Affairs Medical CenterIowa CityUSA

Personalised recommendations