Effects of androgen ablation and vaccine preparation on cancer vaccine efficacy

Cancer vaccines have the advantage of molecular specificity over current treatment modalities such as surgery, chemotherapy and radiation. The immune system is complex and can be modulated by many factors. Vaccine efficacy can be affected by the preparation of the vaccine itself, the addition of adjuvants and the effects of other cancer therapies. In this dissertation, the effects of androgen ablation on a prostate cancer vaccine and the technical preparation of peptide emulsion vaccines are investigated.; First the effects of a standard line of treatment for advanced prostate cancer on a prostate-directed vaccine is examined. Androgens are required for the growth of both normal and neoplastic prostate cells. Androgen ablation results in the apoptosis of the androgen-dependent prostate cancer cells and is used to treat patients with advanced prostate cancer. Androgen ablation results in T and B cells lymphopoeisis, increases thymic output and immune infiltration of the prostate. The current hypothesis in the field is that vaccination should be carried out after androgen ablation and that androgen ablation would improve the responses of the vaccine. Dendritic cells are the most potent antigen-presenting cells and key to successful vaccination strategies, therefore this dissertation deals with the effects of androgen ablation on dendritic cell costimulatory function. Androgen ablation led to an increased activation of dendritic cells in castrated mice but no functional improvements in the costimulation by dendritic cells were found. The hypothesis was disproved and it is concluded that androgen ablation does not improve the immune responses induced by vaccination.; Second, three technical preparations of a peptide emulsion vaccine were compared. Incomplete Freund's adjuvant (IFA) serves as a carrier and an adjuvant for water-in-oil emulsion (W/O) vaccines. The stability of such emulsions greatly affects vaccine efficacy but there is no consensus in the field over which technique would be best to use and no immunological data are available that compare the syringe-extrusion, vortex and homogenizer techniques. I report that all three techniques can be used to prepare peptide-based vaccine emulsions under optimal dose conditions but that the homogenizer or syringe-extrusion may be superior over the vortex technique at suboptimal doses.