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Updated: Jul 17, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Inhibition of prostate carcinogenesis by combined active immunoprophylaxis
Carla De Giovanni1, Stefania Croci, Giordano Nicoletti
1Cancer Research Section, Department of Experimental Pathology, University of Bologna, Bologna, Italy. carla.degiovanni@unibo.it
Abstract:
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.
Insights
This study shows that a novel vaccine combining specific antigens and IL-12 effectively inhibited prostate cancer in mice. This active immunoprophylaxis significantly delayed tumor development, offering a promising strategy for cancer prevention.
Area of Science:
- Oncology
- Immunology
- Preclinical Cancer Research
Background:
- Prostate cancer remains a significant health concern, necessitating novel prevention strategies.
- Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice serve as a valuable model for studying prostate carcinogenesis.
- Active immunoprophylaxis presents a potential avenue for cancer prevention by stimulating the immune system.
Purpose of the Study:
- To evaluate the efficacy of an active immunoprophylactic vaccine in preventing prostate cancer in TRAMP mice.
- To investigate the combined effect of specific antigens and adjuvant stimuli (recombinant IL-12) on prostate carcinogenesis.
- To assess the immune response generated by the vaccine.
Main Methods:
- TRAMP mice were vaccinated with a combination of allogeneic SV40 large T antigen (TAg)-positive cells and recombinant interleukin-12 (IL-12).
- Vaccination commenced in tumor-free mice at 5-6 weeks of age.
- Tumor latency, immune cell responses (CD4, Th1), and antibody production were analyzed.
Main Results:
- The combined vaccine significantly inhibited prostate carcinogenesis, more than doubling the median tumor latency (53 weeks vs. 26 weeks in controls).
- Vaccination with cells alone or IL-12 alone showed limited efficacy (median latency 30 and 39 weeks, respectively).
- The vaccine induced a strong CD4+ T-cell response biased towards the Th1 pathway and generated TAg-specific antibodies.
Conclusions:
- Active immunoprophylaxis using allogeneic TAg-positive cells and IL-12 is a viable strategy to delay prostate cancer in TRAMP mice.
- The combination therapy demonstrates superior efficacy compared to individual components.
- This approach holds potential for preventing SV40 TAg-driven urogenital carcinogenesis.
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