The aim of this study is to investigate whether an active immunoprophylactic approach combining specific antigens and adjuvant stimuli would be able to inhibit prostate carcinogenesis in transgenic TRAMP mice. A vaccine consisting of allogeneic large T antigen (TAg)-positive SV40-transformed cells combined with systemic recombinant IL-12 was administered to TRAMP mice, starting from when they were still tumor-free at 5–6 weeks of age. The combined vaccine significantly inhibited prostate carcinogenesis, giving a more than doubled median latency time of prostatic tumors (53 weeks in comparison to 26 weeks in control mice). Vaccination with cells alone or IL-12 treatment alone was poorly effective (median latency of 30 and 39 weeks, respectively). The combined vaccine induced a very high CD4 response biased toward the Th1 pathway, with the induction of a humoral response that included TAg-specific antibodies. Therefore, such active immunoprophylactic approach based on the combination of allogeneic SV40 TAg-positive cells and systemic administration of recombinant IL-12 significantly delayed autochthonous urogenital carcinogenesis driven by SV40 TAg in TRAMP mice. © 2007 Wiley-Liss, Inc.