Tumor prevention and antitumor immunity with heat shock protein 70 induced by 15-deoxy-Δ^12,14-prostaglandin J₂ in transgenic adenocarcinoma of mouse prostate cells

The biological modifier Δ¹²-prostaglandin J₂ and related prostaglandins have been reported to have significant growth-inhibitory activity with induction of heat shock proteins (Hsps). Tumor-derived Hsps have been shown previously to elicit specific immunity to tumors from which they are isolated. In this study, 15-deoxy-Δ^12,14-prostaglandin J₂ (15d-PGJ₂)-induced Hsp70 was purified from transgenic adenocarcinoma mouse prostate cells (TRAMP-C2). It was then tested for its ability to activate specific CTLs and induce protective immunity against prostate cancer in C57BL/6 mice. Treatment of cells with 8.0 μM 15d-PGJ₂ for 24 h caused significant induction of Hsp70 expression. The yield of Hsp70 purified from 15d-PGJ₂-treated cells was 4-5-fold higher when compared with untreated TRAMP-C2 cells. Vaccination of mice with Hsps isolated from TRAMP-C2 cells elicited tumor-specific CTLs and prevented the growth of TRAMP-C2 tumors. These results indicate that the induced heat shock proteins may have promising applications for antitumor, T-cell immunotherapy. In particular, these findings have important implications for the development of novel anticancer therapies aimed at promoting an immune response to prostate tumors.