title: Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model.
abstract: In a previous study aimed to design a novel prostate cancer vaccine, the authors of the present study demonstrated the advantage of combining the adjuvants Montanide ISA 51 with very small size proteoliposomes (VSSP) to promote a significant humoral immune response to gonadotropin-releasing hormone (GnRH) in healthy animals. The present study compared the efficacy of this vaccine formulation versus the standard treatment currently available in terms of preventing the development of tumors in DD/S mice injected with Shionogi carcinoma (SC) 115 cells. The results demonstrated that 5 non-vaccinated control mice exhibited a fast tumor growth, and succumbed to the disease within 19-31 days. Mice immunized with the GnRH/Montanide ISA 51/VSSP vaccine exhibited a moderate decline in testosterone levels that was associated with a decrease in anti-GnRH antibody titers, which lead to a sustained tumor growth inhibition. In total, 2 mice in the immunized group exhibited complete remission of the tumor for the duration of the present study. In addition, castrated mice, which were used as a control for standard hormonal therapy, exhibited an accelerated decrease in tumor size. However, tumor relapse was observed between days 50 and 54, and between days 65 and 85, following the injection of SC 155 cells. Therefore, these mice were sacrificed at day 90. The present study concludes that the slow and moderate reduction of testosterone levels observed using the GnRH-based vaccine may delay the appearance of castration resistance in a Shionogi prostate cancer model. These findings suggest that this vaccine may be used to delay castration resistance in patients with prostate cancer.
authors.affiliation: Department of Vaccines, Center for Genetic Engineering and Biotechnology, Camagüey, Camagüey 70100, Cuba.
authors.forename: Jesús A Junco
authors.initials: JA
authors.lastname: Barranco
authors.affiliation: Mammal Research Institute and Centre for Neuroendocrinology, University of Pretoria, Pretoria, Gauteng 0028, South Africa; MRC Receptor Biology Unit, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, Western Cape 7925, South Africa.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Millar
authors.affiliation: Department of Vaccines, Center for Genetic Engineering and Biotechnology, Camagüey, Camagüey 70100, Cuba.
authors.forename: Franklin
authors.initials: F
authors.lastname: Fuentes
authors.affiliation: Department of Vaccines, Center for Genetic Engineering and Biotechnology, Camagüey, Camagüey 70100, Cuba.
authors.forename: Eddy
authors.initials: E
authors.lastname: Bover
authors.affiliation: Center for Genetic Engineering and Biotechnology, Havana, Havana 10600, Cuba.
authors.forename: Eulogio
authors.initials: E
authors.lastname: Pimentel
authors.affiliation: Department of Vaccines, Center for Genetic Engineering and Biotechnology, Camagüey, Camagüey 70100, Cuba.
authors.forename: Roberto
authors.initials: R
authors.lastname: Basulto
authors.affiliation: Department of Vaccines, Center for Genetic Engineering and Biotechnology, Camagüey, Camagüey 70100, Cuba.
authors.forename: Lesvia
authors.initials: L
authors.lastname: Calzada
authors.affiliation: Department of Vaccines, Center for Genetic Engineering and Biotechnology, Camagüey, Camagüey 70100, Cuba.
authors.forename: Rolando
authors.initials: R
authors.lastname: Morán
authors.affiliation: Medical University of Camagüey, Camagüey, Camagüey 70100, Cuba.
authors.forename: Ayni
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Center for Genetic Engineering and Biotechnology, Havana, Havana 10600, Cuba.
authors.forename: Hilda
authors.initials: H
authors.lastname: Garay
authors.affiliation: Center for Genetic Engineering and Biotechnology, Havana, Havana 10600, Cuba.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Reyes
authors.affiliation: Department of Vaccines, Center for Genetic Engineering and Biotechnology, Camagüey, Camagüey 70100, Cuba.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Castro
authors.affiliation: Center for Genetic Engineering and Biotechnology, Havana, Havana 10600, Cuba.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Bringas
authors.affiliation: Department of Vaccines, Center for Genetic Engineering and Biotechnology, Camagüey, Camagüey 70100, Cuba.
authors.forename: Niurka
authors.initials: N
authors.lastname: Arteaga
authors.affiliation: Medical University of Camagüey, Camagüey, Camagüey 70100, Cuba.
authors.forename: Henio
authors.initials: H
authors.lastname: Toudurí
authors.affiliation: Department of Vaccines, Center for Genetic Engineering and Biotechnology, Camagüey, Camagüey 70100, Cuba.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rabassa
authors.affiliation: Medical University of Camagüey, Camagüey, Camagüey 70100, Cuba.
authors.forename: Yairis
authors.initials: Y
authors.lastname: Fernández
authors.affiliation: Department of Vaccines, Center for Genetic Engineering and Biotechnology, Camagüey, Camagüey 70100, Cuba.
authors.forename: Andrés
authors.initials: A
authors.lastname: Serradelo
authors.affiliation: Department of Vaccines, Center for Genetic Engineering and Biotechnology, Camagüey, Camagüey 70100, Cuba.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Hernández
authors.affiliation: Center for Genetic Engineering and Biotechnology, Havana, Havana 10600, Cuba.
authors.forename: Gerardo E
authors.initials: GE
authors.lastname: Guillén
keywords: adjuvant combination; castration-resistant prostate cancer; gonadotropin-releasing hormone vaccination; hormone ablation; prostate cancer vaccine