Fuentes F, Junco J, Calzada L, Lopez Y, Pimentel E, Basulto BR, Reyes AO, Garay-Pérez HE, Guillén-Nieto G

Language: English
References: 23
Page: 222-226
PDF size: 266.36 Kb.

ABSTRACT

The effect of different doses of the gonadotropin releasing hormone (GnRH) mimetic peptide GnRHm1-TT is described, administered in three immunization schemes to define the most effective alternative combination for the treatment of prostate cancer. The design elements of the peptide immunogens are the GnRH-m1 linked to a T helper epitope of tetanus toxoid (TT) by chemical synthesis. Three doses of peptide GnRHm1-TT: 125, 300 and 750 µg were formulated in oil-based emulsions and tested in Copenhagen rats. Three immunization schemes (weekly, fortnightly and monthly) were used. As a result, the 750 µg dose generated a specific anti-GnRH antibody response in the fortnightly and monthly schemes, in contrast to 125 µg and 300 µg doses. The anti-GnRH seroconversion in the best responders corresponded with a decline, both in the testosterone levels down to castration and the size and weight of reproductive organs, an effect absent for the remaining doses of the three immunization schemes. The best variant corresponded to the 750 µg dose in a monthly regime. These findings demonstrated a marked immune-neutralization of the GnRH hormone for a subsequent immunological castration.

REFERENCES

1. Garner LL, Campbell GT, Blake CA. Luteinizing hormone (LH)-releasing hormone: chronic effects on LH and follicle-stimulating hormone cells and secretion in adult male rats. Endocrinology. 1990;126(2):992-1000.

2. Ghosh S, Jackson DC. Antigenic and immunogenic properties of totally synthetic peptide-based anti-fertility vaccines. Int Immunol. 1999;11(7):1103-10.

3. Jacobs E, Watson SA, Michaeli D, Ellis IO, Robertson JF. Anti-gonadotrophin releasing hormone antibodies inhibit the growth of MCF7 human breast cancer xenografts. Br J Cancer. 1999;80(3-4):352-9.

4. Talwar GP. Vaccines for control of fertility and hormone-dependent cancers. Immunol Cell Biol. 1997;75(2):184-9.

5. Trewartha D, Carter K. Advances in prostate cancer treatment. Nat Rev Drug Discov. 2013;12(11):823-4.

6. Ladd A, Tsong YY, Lok J, Thau RB. Active immunization against LHRH: I. Effects of conjugation site and dose. Am J Reprod Immunol. 1990;22(1-2):56-63.

7. Javid A, Ganaie M, Phil V, Shrivastava K. The effect of active immunization with gonadotropin releasing hormone conjugate (GnRH-BSA) ongonadosomatic indices (GSI) and sperm parameters in mice. Iranian J Reprod Med. 2008:6:119-23.

8. Cook RB, Popp JD, Kastelic JP, Robbins S, Harland R. The effects of active immunization against gnRH on testicular development, feedlot performance, and carcass characteristics of beef bulls. J Animal Sci. 2000;78(11):2778-83.

9. D’Occhio MJ, Aspden WJ, Trigg TE. Sustained testicular atrophy in bulls actively immunized against GnRH: potential to control carcase characteristics. Anim Reprod Sci. 2001;66(1-2):47-58.

10. Zeng XY, Turkstra JA, van de Wiel DF, Guo DZ, Liu XY, Meloen RH, et al. Active immunization against gonadotrophinreleasing hormone in Chinese male pigs. Reprod Domest Anim. 2001;36(2):101-5.

11. Basulto R, Milanes C, Rojas A, Fuentes F, Izquierdo N, Bertot JA. Effects of GnRH immunization in the testicular structure and function of adults dogs. Biotecnol Apl. 2003;20:20-4.

12. Junco JA, Basalto R, Fuentes F, Bover E, Reyes O, Pimentel E, et al. Gonadotrophin releasing hormone-based vaccine, an effective candidate for prostate cancer and other hormone-sensitive neoplasms. Adv Exp Med Biol. 2008;617:581-7.

13. Finstad CL, Wang CY, Kowalski J, Zhang M, Li ML, Li XM, et al. Synthetic luteinizing hormone releasing hormone (LHRH) vaccine for effective androgen deprivation and its application to prostate cancer immunotherapy. Vaccine. 2004;22(9-10):1300-13.

14. Turkstra JA, van der Meer FJ, Knaap J, Rottier PJ, Teerds KJ, Colenbrander B, et al. Effects of GnRH immunization in sexually mature pony stallions. Anim Reprod Sci. 2005;86(3-4):247-59.

15. Xu J, Zhu Z, Wu J, Liu W, Shen X, Zhang Y, et al. Immunization with a recombinant GnRH vaccine conjugated to heat shock protein 65 inhibits tumor growth in orthotopic prostate cancer mouse model. Cancer Lett. 2008;259(2):240-50.

16. Bringas R, Basulto R, Reyes O, de La Fuente J. Vaccine for the reversible immunocastration of mammals. Patent number: WO 9827111. 1998 Jun 25.

17. Fields GB, Noble RL. Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int J Pept Protein Res. 1990;35(3):161-214.

18. Aguilar FF, Barranco JJ, Fuentes EB, Aguilera LC, Saez YL, Santana MD, et al. Very small size proteoliposomes (VSSP) and Montanide combination enhance the humoral immune response in a GnRH based vaccine directed to prostate cancer. Vaccine. 2012;30(46):6595-9.

19. Oonk HB, Turkstra JA, Schaaper WM, Erkens JH, Schuitemaker-de Weerd MH, van Nes A, et al. New GnRH-like peptide construct to optimize efficient immunocastration of male pigs by immunoneutralization of GnRH. Vaccine. 1998;16(11-12):1074-82.

20. Miller LA, Johns BE, Elias DJ, Crane KA. Comparative efficacy of two immunocontraceptive vaccines. Vaccine. 1997;15(17- 18):1858-924.

21. Jayashankar R, Chaudhuri MK, Singh O, Alam A, Talwar GP. Semisynthetic anti-LHRH vaccine causing atrophy of the prostate. Prostate. 1989;14(1):3-117.

22. Jinshu X, Jingjing L, Duan P, Zheng Z, Ding M, Jie W, et al. A synthetic gonadotropin- releasing hormone (GnRH) vaccine for control of fertility and hormone dependent diseases without any adjuvant. Vaccine. 2005;23(40):4834-43.

23. Ornstein DK, Dahut WL, Liotta LA, Emmert-Buck MR. Review of AACR meeting: new research approaches in the prevention and cure of prostate cancer, 2-6 December 1998, Indian Wells, CA. Biochim Biophys Acta. 1999;1424(1):R11-9.