Induction of PSA-specific CTLs and anti-tumor immunity by a genetic prostate cancer vaccine.

Prostate cancer is the most common malignancy in Swedish and American men. Effective curative treatment modalities are debilitating and available only for localized disease. As an immunotherapy approach, DNA encoding prostate-specific antigen (PSA), was used to immunize mice and induce PSA-specific cellular immunity. A plasmid expressing PSA, alone or in combination with plasmids coding for GM-CSF and/or IL-2, was used for DNA immunization. Cr-release, intracellular IFN-gamma cytokine staining, and tumor challenge assays were used to evaluate the immune response. The DNA vaccine induces PSA-specific cytotoxic T lymphocytes (CTLs) and when co-injected with IL-2 and GM-CSF it protects four of five mice against a PSA-expressing tumor challenge. We demonstrate that immunization with a PSA DNA vaccine can evoke PSA-specific cellular immune responses. We also show, for the first time, that a PSA DNA vaccine can induce anti-tumor immunity in vivo.

Roos AK ，Pavlenko M ，Charo J ，Egevad L ，Pisa P ... -  《PROSTATE》

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》

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 ... -  《-》

Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine.

Kim JJ ，Trivedi NN ，Wilson DM ，Mahalingam S ，Morrison L ，Tsai A ，Chattergoon MA ，Dang K ，Patel M ，Ahn L ，Boyer JD ，Chalian AA ，Schoemaker H ，Kieber-Emmons T ，Agadjanyan MA ，Weiner DB ... -  《ONCOGENE》

CpG oligonucleotide as an adjuvant for the treatment of prostate cancer.

Lubaroff DM ，Karan D 《-》