Anti-GnRH Neutralizing Antibodies Produce Testosterone Ablation and Tumor Shrinkage in Prostate Cancer Models
Author(s): 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
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.