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.
BACKGROUND
Prostate cancer is currently the most commonly diagnosed cancer in men and the second leading cause of cancer-related death in men in the US. Immunological approaches may provide an alternative option for prevention and treatment of prostate cancer.


METHODS
To develop vaccine against prostate cancer using mouse model, we constructed three recombinant adenoviruses expressing prostate-specific membrane antigen (rAd/PSMA), prostate stem cell antigen (rAd/PSCA) and six-transmembrane epithelial antigen of the prostate (rAd/STEAP), that were specifically up-regulated in the transgenic murine prostate cancer.


RESULTS
Male C57BL/6 mice were immunized by intravenous injection of these recombinant adenoviruses and subsequently by subcutaneous injection of dendritic cells pulsed with TRAMP-C1 tumor lysate. After subcutaneous challenge with TRAMP-C1 cells, tumor growth was significantly delayed in the immunized mice compared to the control group. Surprisingly, significant numbers of STEAP-specific CD8 T cells were detected in the peripheral blood and the spleen of immune mice using MHC I tetramers, and injection of rAd/STEAP alone followed by pulsed DC was sufficient to inhibit tumor growth. Therapeutic vaccination also significantly delayed the growth of pre-established tumors.


CONCLUSIONS
Our results suggest that STEAP is a good immunologic target antigen against prostate cancer and our vaccination regimen successfully elicits anti-tumor CTL responses and suppresses tumor growth. More studies will expedite the development of this vaccine toward clinical application.
Kim
Sol
S
Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea.
Lee
Jee-Boong
JB
Lee
Geon Kook
GK
Chang
Jun
J
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D015316:Genetic Therapy / Q000379:methods; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D017430:Prostate-Specific Antigen / Q000235:genetics* / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C504399:Psca protein, mouse; C486624:Steap protein, mouse; D019444:Vaccines, DNA; D017430:Prostate-Specific Antigen