Related Experiment Video
Updated: Jul 12, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
A novel murine model of allogeneic vaccination against prostate cancer
M-C Labarthe1, P Theocharous, N Russell
1Department of Oncology, Cellular and Molecular Medicine, St George's University of London, Cranmer Terrace, London SW17 0RE, UK. mlabarth@sgul.ac.uk
Abstract:
Prostate cancer continues to be a major cause of death in men. Surgical and medical treatments of the disease have improved, but metastasic disease remains a significant clinical problem. Novel therapies such as whole cell vaccination offer the potential of treating disease by stimulating the immune system. To study the efficacy of a whole cell vaccine in prostate cancer two strains of mice were used: C57BL/6 (H-2Kb) and C3H/HeJ (H-2K(k)) in combination with four different cell lines. Thus, a model was constructed of allogeneic and syngeneic vaccine, as well as a challenge tumour for each strain. Two novel cell lines were developed during this study. Firstly, the non tumourigeneic PMC-1 was derived from a normal mouse prostate and immortalized with HPV16. Secondly, the tumourigeneic PMC-1 C6ras1p1 was transformed with human ras gene which formed tumours in both SCID and C3H/HeJ mice. Protection, and the nature of the immune response to syngeneic and allogeneic vaccine, in males and females was examined in both strains. Vaccination with both syngeneic and allogeneic irradiated whole cell vaccines induced protection from syngeneic challenge in females. However, no protection was observed when allogeneic vaccine was given to male mice. This correlated with the immune response. Two types of cellular immune responses were generated in females. A NK-mediated response was observed in C57BL/6 mice, whilst C3H/HeJ mice developed a CTL response. Little or no cellular immune response was observed in males. The cytokine profile in C3H/HeJ females was a mixture of Th1 and Th2 whilst a mainly Th1 profile was observed in C57BL/6 mice. Male mice showed a diminished cytokine secretion compared to females which was further depressed after challenge. The difference in immunity was largely as expected, since tolerance to prostate antigens should not normally develop in female mice. However, this makes this model particularly relevant clinically since it directly mimics the human situation and thus may accelerate the development of whole cell vaccines for clinical use.
Insights
Whole cell vaccination shows promise for prostate cancer treatment. Female mice developed immune responses and protection against tumors, unlike males, suggesting a clinically relevant model for human therapy.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Prostate cancer remains a significant cause of mortality in men, with metastatic disease posing a major clinical challenge.
- Whole cell vaccination is an emerging therapeutic strategy that stimulates the immune system to combat cancer.
- Developing effective vaccine models is crucial for advancing prostate cancer treatment.
Purpose of the Study:
- To evaluate the efficacy of whole cell vaccination in a preclinical prostate cancer model.
- To investigate the sex-specific immune responses to syngeneic and allogeneic vaccines.
- To establish a relevant animal model for testing novel prostate cancer immunotherapies.
Main Methods:
- Developed novel mouse prostate cell lines (PMC-1, PMC-1 C6ras1p1) for vaccine and tumor challenge models.
- Utilized two mouse strains (C57BL/6, C3H/HeJ) to assess syngeneic and allogeneic vaccine efficacy.
- Examined protection, cellular immune responses (NK, CTL), and cytokine profiles (Th1/Th2) in male and female mice.
Main Results:
- Female mice vaccinated with syngeneic or allogeneic irradiated whole cell vaccines showed protection against tumor challenge.
- Male mice exhibited little to no protective immune response following vaccination.
- Distinct immune responses were observed in females: NK-mediated in C57BL/6 and CTL in C3H/HeJ mice, with varied cytokine profiles.
Conclusions:
- Whole cell vaccination can induce protective immunity in female mice against prostate cancer.
- Sex-based differences in immune response are significant, with males showing diminished responses.
- The developed model mimics the human situation, potentially accelerating clinical development of whole cell vaccines for prostate cancer.
