title: A novel murine model of allogeneic vaccination against prostate cancer.
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.
authors.affiliation: Department of Oncology, Cellular and Molecular Medicine, St George's University of London, Cranmer Terrace, London SW17 0RE, UK. mlabarth@sgul.ac.uk
authors.forename: M-C
authors.initials: MC
authors.lastname: Labarthe
authors.forename: P
authors.initials: P
authors.lastname: Theocharous
authors.forename: N
authors.initials: N
authors.lastname: Russell
authors.forename: S
authors.initials: S
authors.lastname: Todryk
authors.forename: C
authors.initials: C
authors.lastname: Bangma
authors.forename: P
authors.initials: P
authors.lastname: Thraves
authors.forename: A G
authors.initials: AG
authors.lastname: Dalgleish
authors.forename: M A
authors.initials: MA
authors.lastname: Whelan
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D027383:Papillomaviridae / Q000276:immunology; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D014611:Vaccination / Q000379:methods*