Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

Junco Barranco,Jesús  A.; Millar,Robert  P.; Fuentes,Franklin; Bover,Eddy; Pimentel,Eulogio; Basulto,Roberto; Calzada,Lesvia; Morán,Rolando; Rodríguez,Ayni; Garay,Hilda; Reyes,Osvaldo; Castro,Maria  D.; Bringas,Ricardo; Arteaga,Niurka; Toudurí,Henio; Rabassa,Mauricio; Fernández,Yairis; Serradelo,Andrés; Hernández,Eduardo; Guillén,Gerardo  E.

doi:10.3892/ol.2016.4679

Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

Authors:
- Jesús A. Junco Barranco
- Robert P. Millar
- Franklin Fuentes
- Eddy Bover
- Eulogio Pimentel
- Roberto Basulto
- Lesvia Calzada
- Rolando Morán
- Ayni Rodríguez
- Hilda Garay
- Osvaldo Reyes
- Maria D. Castro
- Ricardo Bringas
- Niurka Arteaga
- Henio Toudurí
- Mauricio Rabassa
- Yairis Fernández
- Andrés Serradelo
- Eduardo Hernández
- Gerardo E. Guillén
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Affiliations: Department of Vaccines, Center for Genetic Engineering and Biotechnology, Camagüey, Camagüey 70100, Cuba, Mammal Research Institute and Centre for Neuroendocrinology, University of Pretoria, Pretoria, Gauteng 0028, South Africa, Center for Genetic Engineering and Biotechnology, Havana, Havana 10600, Cuba, Medical University of Camagüey, Camagüey, Camagüey 70100, Cuba
Published online on: June 7, 2016 https://doi.org/10.3892/ol.2016.4679
Pages: 963-970

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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.

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