Gonadotrophin releasing hormone-based vaccine, an effective candidate for prostate cancer and other hormone-sensitive neoplasms.
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 [0.05 nM 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 GnRHm1-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 GnRHm1-TT vaccine may be a potential candidate in the treatment of PC, BC, and other hormone-dependent cancers.
Junco
Jesús A
JA
Center for Genetic Engineering and Biotechnology of Camaguey, Camaguey, Cuba.
Basalto
Roberto
R
Fuentes
Franklin
F
Bover
Eddy
E
Reyes
Osvaldo
O
Pimentel
Eulogio
E
Calzada
Lesvia
L
Castro
Maria D
MD
Arteaga
Niurka
N
López
Yovisleidis
Y
Hernández
Héctor
H
Bringas
Ricardo
R
Garay
Hilda
H
Peschke
Peter
P
Bertot
José
J
Guillén
Gerardo
G
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D004285:Dogs; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007167:Immunotherapy; D008297:Male; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D051381:Rats; D013552:Swine; D013745:Tetanus Toxoid / Q000627:therapeutic use; D014614:Vaccines, Synthetic / Q000627:therapeutic use
D019496:Cancer Vaccines; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic; D007987:Gonadotropin-Releasing Hormone