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Anti-GnRH Neutralizing Antibodies Produce Testosterone Ablation and Tumor Shrinkage in Prostate Cancer Models

Jesús A. Junco, Franklin Fuentes, Lesvia Calzada, Eddy Bover, Eulogio Pimentel, Yovisleidis López, Roberto Basulto, Hilda Garay, Osvaldo Reyes, Angel Cid-Arregui, Maria D. Castro, Rafael Martínez, Niurka Arteaga, Ana Campal, Ayni Rodríguez, Andrés Serradelo, Eduardo Hernández, Mirialis Arias, Raúl González, Matilde López, Gisell Bebert, Gerardo Guillén
Journal of Cancer Science and Clinical Therapeutics , Volume 4, pp 333-348; doi:10.26502/jcsct.5079076

Abstract: Background: Vaccines based on modified GnRH peptide variants can be an alternative treatment for advanced prostate cancer. However, the efficacy of the GnRH-based vaccine variants has been limited by their insufficient immunogenicity. Methods: The current vaccine based on the modified peptide GnRHm1-TT peptide has been formulated in the different oil adjuvants; Montanide ISA 51 and Montanide ISA 51VG. Results: Experiments carried out in healthy animal models demonstrated to produce significant anti-GnRH antibody levels (p<0.01) that led to testosterone ablation (p<0.001), and in correspondence produced prostate atrophy (p<0.001). Here, it has been also studied the effect of different GnRHm1-TT peptide doses on its efficacy in different healthy animals. The immunization of Copenhagen rats implanted with the hormone-sensitive autologous Dunning R3327-H prostate tumor caused inhibition of prostate tumor growth in and resulted in over two-fold increase in survival compared to placebo (p<0.01). In vitro studies in the COS-7-ratGnRH model using sera from healthy animals immunized with the GnRHm1-TT/Montanide ISA 51VG vaccine candidate, proved that the anti-GnRH antibodies generated were able to neutralize natural GnRH hormone and inhibit signaling through its receptor. Conclusions: We conclude that the GnRHm1-TT peptide formulated in Montanide ISA 51 VG is a suitable vaccine candidate that induce an effective anti GnRH immune response in different animal species and in correspondence produce a significant drop of testosterone levels, atrophy of prostate and tumor shrinkage in the Dunning R3327-H tumor model.
Keywords: Antibody / vaccine / Efficacy / model / tumor / Prostate / Dunning R3327 / Neutralize / ISA 51VG

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