Prevention of de novo prostate cancer by immunization with tumor-derived vaccines

Since advanced prostate cancer is difficult to treat, we have chosen a very different approach: the development of vaccines to prevent initial de novo tumor formation. To test the hypothesis that prostate cancer can be prevented by vaccination, Lobund–Wistar (LW) rats were vaccinated subcutaneously with complete Freund’s adjuvant (CFA) plus glutaraldehyde-fixed (GFT) whole cell or potassium thiocyanate extract (PTE) preparations derived from in vivo tumors, or with media and CFA (media-vaccinated). Rats were vaccinated each month substituting incomplete Freund’s adjuvant for CFA, from age 3 to 12 months, and methylnitrosourea (30 mg/kg) was administered intravenously at 4 months of age. Groups of 30 GFT cell–vaccinated rats showed a 90% reduction, and PTE-vaccinated rats, a 50% reduction in the occurrence of de novo prostate tumors compared with media-vaccinated controls. When splenocytes from vaccinated rats were incubated with tumor cells prior to subcutaneous implantation, PTE-vaccinated rats showed a 80% reduction, and GFT cell–vaccinated rats showed a 40% reduction in the occurrence of tumors, demonstrating a role for the spleen in the protective response. The inflammatory responses in tumors from GFT cell–vaccinated rats and PTE-vaccinated rats were distinguished by an influx of eosinophils compared with the responses in tumors from media-vaccinated rats. These results demonstrate the possibility that prostate cancer can be prevented by immunization with vaccines based on whole tumor–derived vaccines.