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Gonadotrophin Releasing Hormone-Based Vaccine, an Effective Candidate for Prostate Cancer and Other Hormone-sensitive Neoplasms

  • Jesús A. Junco
  • Roberto Basalto
  • Franklin Fuentes
  • Eddy Bover
  • Osvaldo Reyes
  • Eulogio Pimentel
  • Lesvia Calzada
  • Maria D. Castro
  • Niurka Arteaga
  • Yovisleidis López
  • Héctor Hernández
  • Ricardo Bringas
  • Hilda Garay
  • Peter Peschke
  • José Bertot
  • Gerardo Guillén
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)

Summary

Prostate growth, development, functions, and neoplastic transformation is androgen dependent. Estrogens have similar effects in the ovary and breast. Previous studies using gonadotrophin releasing hormone (GnRH/LHRH) vaccines have shown the usefulness of immunization against this hormone in prostate (PC) and breast cancer (BC). We have synthesized a peptide mutated at position 6 and attached to the 830–844 tetanic toxoid (TT) helper T cell sequence in the same synthesis process. After repeated pig immunizations, we have demonstrated a vaccine that significantly decreased testes size (p < 0.001), prostate (p < 0.01), seminal vesicles (p < 0.01), and testosterone (T) castration [0.05nM ml−1 (p < 0. 01)]. Similar results were obtained in adult male and female healthy dogs and Macaca fascicularis models. These data indicate that this GnRHml-TT vaccine is safe and able to induce significant tumor growth inhibition in the Dunning R3327-H rat androgen responsive prostate tumor model. In these rats, the immunization induced high anti-GnRH titers concomitant with T castration reduction (p < 0.01) in 90% of the animals tested. In addition, 70% of the responders exhibited tumor growth inhibition (p = 0.02) and a survival rate approximately three times longer that those of untreated rats. These data indicate that GnRHml-TT vaccine may be a potential candidate in the treatment of PC, BC, and other hormone-dependent cancers.

Keywords

Breast Cancer Luteinizing Hormone Release Hormone Effective Candidate Cell Sequence Boar Taint 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Hougten RA, De Graw ST, Bray MK, et al. (1986) Simultaneous multiple peptide Synthesis: The rapid preparation of large numbers of discrete peptides for biological, immunological and methodologicals studies. Biotecniques; 4:522–526.CrossRefGoogle Scholar
  2. 2.
    Finstad CL, Wang CY, Kowalsky J, et al. (2004) Synthetic luteinizing hormone releasing hormone (LHRH) vaccine for effective androgen deprivation and its application to prostate cancer immunotherapy. Vaccine; 22:1300–1313.PubMedCrossRefGoogle Scholar
  3. 3.
    Basulto R, Milanés C, Rojas A, et al. (2003) Effects of GnRH immunization in the testicular structure and function of adult dogs. Biotecnología Aplicada; 20:20–24.Google Scholar
  4. 4.
    Subash S, Chaujan VS, Arunan K, et al. (1993) Synthetic Gonadotrophin-releasing hormone (GnRH) vaccines incorporating GnRH and synthetic T helper epitopes. Vaccine; 11:1145–1150.CrossRefGoogle Scholar
  5. 5.
    Hoskinson RM, Rigby RDG, Mattner PE, et al. (1990) Vaxstrate: An anti-reproductive vaccine for cattle. Australian Journal of Biotechnology; 4:166–170.PubMedGoogle Scholar
  6. 6.
    Simms MS, Schofield DP, Jacobs E, et al. (2000) Anti GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer. British Journal of Cancer; 83:443–446.PubMedCrossRefGoogle Scholar
  7. 7.
    Fraomme B, Eftekhari P, van Regenmontel M, et al. (2003) A novel retro-inverso gonadotropin-releasing hormone (GnRH) immunogen elicits antibodies that neutralize the activity of native GnRH. Endocrinology; 144:73262–73269.Google Scholar
  8. 8.
    Paul. WE (1993) Fundamental Immunology, 3rd ed. Chapter 32 pp. 1143–1178. Reven Press, Ltd., 1185, New York.Google Scholar
  9. 9.
    Fuerst J, Fiebiger E, Jungwirth A, et al. (1997) Effect of active immunization against luteinizing hormone releasing hormone on the androgen sensitive Dunning R3327-PAP and androgen-independent Dunning R3327-AT2.1 prostate cancer sublines. Prostate; 32:77–84.PubMedCrossRefGoogle Scholar
  10. 10.
    Ladd A, Tsong YY, Prabhu G, et al. (1998) Effects of long term immunization against LHRH and androgen treatment on gonadal function. Journal of Reproductive Immunology; 15:85.CrossRefGoogle Scholar
  11. 11.
    Oonk HB, Turkstra JA, Schaaper WM, et al. (1998) New GnRH-like peptide construct to optimize efficient immunocastration of male pigs by immunoneutralization of GnRH. Vaccine; 36:64–67.Google Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Jesús A. Junco
    • 1
  • Roberto Basalto
  • Franklin Fuentes
  • Eddy Bover
  • Osvaldo Reyes
  • Eulogio Pimentel
  • Lesvia Calzada
  • Maria D. Castro
  • Niurka Arteaga
  • Yovisleidis López
  • Héctor Hernández
  • Ricardo Bringas
  • Hilda Garay
  • Peter Peschke
  • José Bertot
  • Gerardo Guillén
  1. 1.Center for Genetic Engineering and Biotechnology of CamagueyCamagueyCuba

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