Heberprovac is a GnRH based vaccine candidate containing 2.4 mg of the GnRHm1-TT peptide as the main active principle; 245 μg of the very small size proteoliposomes adjuvant (VSSP); and 350 μL of Montanide ISA 51 VG oil adjuvant. The aim of this study was to assess the safety and tolerance of the Heberprovac in advanced prostate cancer patients as well as its capacity to induce anti-GnRH antibodies, the subsequent effects on serum levels of testosterone and PSA and the patient overall survival. The study included eight patients with histologically-proven advanced prostate cancer with indication for hormonal therapy, who received seven intramuscular immunizations with Heberprovac within 18 weeks. Anti-GnRH antibody titers, testosterone and PSA levels, as well as clinical parameters were recorded and evaluated. The vaccine was well tolerated. Significant reductions in serum levels of testosterone and PSA were seen after four immunizations. Castrate levels of testosterone were observed in all patients at the end of the immunization schedule, which remained at the lowest level for at least 20 months. In a 10-year follow-up three out of six patients who completed the entire trial survived. In contrast only one out eight patients survived in the same period in a matched randomly selected group receiving standard anti-hormonal treatment. Heberprovac vaccination showed a good security profile, as well as immunological, biochemical and, most importantly, clinical benefit. The vaccinated group displayed survival advantage compared with the reference group that received standard treatment. These results warrant further clinical trials with Heberprovac involving a larger cohort.

Prostate cancer is the most commonly diagnosed malignancy in men in the Western Hemisphere, with 33% incidence rate and the second leading cause of cancer death in men, exceeded only by lung cancer despite the efforts to achieve early diagnosis of disease through the use of the serological marker "prostate specific antigen" (PSA). Worldwide, there are about 650 000 reported new cases of prostate cancer each year and a mortality of about 200 000 cases. Autopsy studies in men show that 70% of men develop prostate cancer sometime in their lives, although many of them are clinically irrelevant (Russel et al, 1994; Cancer Statistics, 2008). Prostate cancer is diagnosed in a clinically relevant stage in one out of six men around the world and is usually diagnosed by elevated levels of prostate specific antigen (PSA) or the presence of an abnormal digital rectal examination. The Prostate Specific Antigen (PSA), is a protein produced by normal and pathological prostate cells. This protein is found in relatively small levels in the bloodstream of men with normal prostate, however, is considerably increased in most individuals suffering from a malignant disease of the prostate, but also tends to increase in benign diseases of the gland such as prostatitis and benign prostatic hyperplasia (BPH). While assessing the levels of PSA takes into account the individual's age, it is generally considered that these values may reach up to 4 ng/mL (Sonpavde et al, 2010). Unfortunately, however, the PSA does not distinguish between the stages of the disease. 3. Prostatic tumurogenesis Prostate cancer seems to develop over a period ranging from 20 to 30 years (Kabalin et al, 1989; Sacker et al, 1996). In most cases, the tumurogenesis begins as a prostatic inflammatory atrophy which progresses to prostatic intraepithelial neoplasia (PIN), which in some cases leads to carcinoma (De Marzo et al 2003, Nelson et al, 2007). In addition to genetic changes occurred, androgens act as promoters of proliferation and prostate growth. Thus, testosterone passes into the prostate cell where the action of the enzyme 5 alpha reductase is converted to its metabolically active form, dihydrotestosterone (DHT). Once DHT binds to the receptor in the cytoplasm, this favors the formation of dimers crossing the nuclear membrane where the complex binds to genes with androgen-responsive elements, a process modulated by co-activators and co-repressors (You and Tindall, 2004).