The influence of different peptide combinations to increase the immunogenicity of the Gonadotrophin Releasing Hormone Vaccine for prostate cancer treatment.

PURPOSE: Therapeutic vaccines, specifically the Gonadotrophin Releasing Hormone (GnRH) vaccine, are considered an additional therapeutic option for advanced stage prostate cancer. Our work showed amplification of the immune response when combining two peptides with and without the Very Small Size Proteoliposomes (VSSP). VSSP is a potent adjuvant for dendritic cells activation and Th1 differentiation. as enhanced immune response. METHODS: The test was carried out in Copenhagen rats as animal model. RESULTST: The use of both peptides and their combination with VSSP generated a potentiation of the immune response statistically superior, in term of generating anti GnRH antibody and effects on target organs, when it was compared with the effects which occurs with independent peptides and with and without the VSSP. These results can find application in the development of GnRH vaccine candidates and in peptide based vaccine strategies. CONCLUSIONS: Immunization with the peptide combination enhances the immune response when mixed with the VSSPs.

Very small size proteoliposomes (VSSP) and Montanide combination enhance the humoral immuno response in a GnRH based vaccine directed to prostate cancer.

Very small size proteoliposomes (VSSP) constitute a complex of very small size proteoliposomes that includes proteins, lipids, CpG and gangliosides tumor-associated that provides a potential target for cancer immunotherapy. This compound has been described to stimulate the humoral and cellular response, dendritic cells (DC) activation and differentiation of T-helper cells, specially, in immunocompromised patients with cancer status. This work deals with the stimulating capacity of the VSSP to reach a humoral response when they are used as a component in a peptidic vaccine based on the gonadotrophin releasing hormone (GnRH). This study was carried out in male Copenhagen rats, which were immunized with 750µg of the GnRH mimetic peptide (GnRHm1-TT) with or without the VSSP. The mixtures were always emulsified with the oil adjuvant Montanide ISA 51. The anti GnRH seroconversion analysis revealed that the group immunized with the peptide GnRHm1-TT/VSSP developed a strong anti GnRH seroconversion. These antibody levels proved to be significant superior to those reached by the use of the GnRHm1-TT peptide solely emulsified in Montanide. Post-mortem analysis on the Testosterone ablation target organs (prostate and testicles) yielded a sudden decrease in their size and weight in respect to the control group. On the other hand, the group submitted to the use of GnRHm1-TT/VSSP, showed a significant difference in the reduction of these target organs in comparison with the group only immunized with GnRHm1-TT adjuvated in Montanide ISA 51. These values turned to be of p=0.023 and p=0.009 in the prostate and testicles respectively. These findings foreground the VSSP as a useful immunopotentiator to be used as part of a GnRH based vaccine to treat prostate cancer.