Tissue vaccines for prevention and treatment of prostate cancer

Tissue vaccines are produced from harvested tumor material and contain a tremendously large menu of antigens, including those expressed only during in vivo growth and those associated with tumor stroma. Production of tissue vaccines from xenogeneic sources not only presents a means to overcome immunologic tolerance of tumors, but also represents a means to greatly expand availability of vaccine raw material compared to autologous vaccines. To determine if vaccination with tissue vaccines is a potential strategy for prevention and treatment of prostate cancer, we evaluated the utility of tissue vaccines derived from glutardehyde-fixed tumor (GFT) tissue and potassium thiocyanate extract (PTE) of tumor tissue. Subcutaneous tumors generated in Lobund-Wistar (LW) rats with the PAIII prostate cancer line were harvested, dissociated, and treated with 3% glutaraldehyde or prepared as an extract with potassium thiocyanate. To evaluate prevention of prostate cancer, groups of thirty LW rats were treated with intravenous methylnitrosourea (30 mg/kg) to induce autochthonous prostate tumors and were then vaccinated subcutaneously (SC) monthly from 2 to 10 months of age with either media (MEM), GFT or PTE. At 12 months of age, gross and histological examination of prostates showed 50% and 90% reductions in the incidence of prostate cancer in PTE- and GFT-vaccinated rats, respectively, compared to media-vaccinated controls (Fig. 1). Using the same model, groups of rats underwent weekly vaccination with MEM or GFT when palpable tumors were first detected in the caudal abdomen to evaluate the utility of tissue vaccines as a treatment for prostate cancer. Though size of the primary tumor was not significantly reduced, 70% of GFT-vaccinated rats were free of metastasis compared to only 10% of controls (Fig. 2). To determine if this vaccine could be used as a xenogeneic preparation for human prostate cancer, immunocompetent Ncr-Foxn1<nu> mice were vaccinated SC with the GFT vaccine; their splenocytes harvested 7 days after the last boost and co-incubated with human PC346 prostate cancer cells (Group 1); and orthotopically transplanted into syngeneic BALB/c nu/nu mice. Groups of 20 nu/nu mice were treated this way or with PC346 cells co-incubated with splenocytes from media-vaccinated mice (Group 2); or transplanted with untreated PC346 cells (Group 3). Ten weeks later, the mice were euthanized and prostates evaluated for tumor growth. The incidence of prostate cancer was reduced by 70% in Group 1 mice compared to those in Groups 2 and 3, indicating that this vaccine has xenogeneic efficacy. In summary, tissue vaccines represent a means to harvest numerous powerful and novel antigens which cannot be captured in any other way, and which can be effectively used to prevent and treat prostate cancer.