Vaccination with a DNA vaccine based on human PSCA and HSP70 adjuvant enhances the antigen-specific CD8+ T-cell response and inhibits the PSCA+ tumors growth in mice.

DNA vaccines have been shown to be an effective approach to induce antigen-specific cellular and humoral immunity. However, the lower immune intensity in clinical trials limits the application of DNA vaccine. Here we intend to develop a new DNA vaccine based on prostate stem-cell antigen (PSCA), which has been suggested as a potential target for prostate cancer therapy, and enhance the DNA vaccine potency with heat shock proteins (HSPs) as adjuvant. A series of DNA plasmids encoding human PSCA, human HSP70 and their conjugates was constructed and injected into male mice intramuscularly (i.m.). To evaluate the immune responses and therapeutic efficacy of these plasmids, major histocompatibility complex (MHC)-restricted PSCA and HSP70-specific epitopes were predicted and a mouse model with a human PSCA-expressing tumor was constructed. The result showed that mice vaccinated with PSCA-HSP plasmids generated the strongest PSCA-specific CD8+ T-cell immune response, but the CD4+ TH1 and TH2 cell immune responses were similar with those vaccinated with other HSP-adjuvant PSCA plasmids or only PSCA DNA. The immunity of HSP70 was also observed and the mice i.m. injected with PSCA+ HSP mixed plasmids generated the lowest anti-HSP antibodies. Furthermore, these vaccinations inhibited the growth of PSCA-expressing tumors and prolonged mouse survival. These observations emphasize and extend the potential of the human HSP70 gene as adjuvant for DNA vaccines, and the vaccine based on PSCA and HSP70 is of potential value for treating prostate cancer.

Zhang X ，Yu C ，Zhao J ，Fu L ，Yi S ，Liu S ，Yu T ，Chen W ... -  《JOURNAL OF GENE MEDICINE》

Prostate stem cell antigen vaccination induces a long-term protective immune response against prostate cancer in the absence of autoimmunity.

Garcia-Hernandez Mde L ，Gray A ，Hubby B ，Klinger OJ ，Kast WM ... -  《-》

Vaccination with recombinant adenoviruses and dendritic cells expressing prostate-specific antigens is effective in eliciting CTL and suppresses tumor growth in the experimental prostate cancer.

Kim S ，Lee JB ，Lee GK ，Chang J ... -  《-》

Dual antigen target-based immunotherapy for prostate cancer eliminates the growth of established tumors in mice.

Karan D ，Dubey S ，Van Veldhuizen P ，Holzbeierlein JM ，Tawfik O ，Thrasher JB ... -  《-》

Vaccination with a chaperone complex based on PSCA and GRP170 adjuvant enhances the CTL response and inhibits the tumor growth in mice.

Increasing knowledge demonstrate that prostate stem cell antigen (PSCA) is a promising candidate for immunotherapy of advanced prostate cancer. However, tumor escape with down-regulation of target antigens may limit the susceptibility of tumor cells to the immune attack. Concomitant generation of T-cell responses against several immunodominant antigens may circumvent this potential drawback. In this study, we prepared the chaperone complex vaccine based on PSCA and GRP170, and utilized it to immunize the C57BL/6 mice. In addition, the T-cell response was monitored with ELISPOT and (51)Cr-release assays, and the tumor growth and the life span of tumor-bearing mice were assessed. The results demonstrated the chaperone complex based on PSCA and GRP170 could enhance the T-cell mediate immune responses, which significantly inhibited the tumor growth and prolonged the life span of tumor-bearing mice. In conclusion, our findings supported the strategy of chaperone complex, based on PSCA and GRP170, could be an effective treatment for prostate cancer therapy.

Huo W ，Ye J ，Liu R ，Chen J ，Li Q ... -  《-》