Combination immunotherapy of primary prostate cancer in a transgenic mousemodel using CTLA-4 blockade

We have previously shown that antibodies to CTLA-4, an inhibitory receptor on T cells, can be effective at inducing regression of transplantable murin e tumors. In this study, we demonstrate that an effective immune response a gainst primary prostate tumors in transgenic (TRAMP) mice can be elicited u sing a strategy that combines CTLA-4 blockade and an irradiated tumor cell vaccine. Treatment of TRAMP mice at 14 Reeks of age resulted in a significa nt reduction in tumor incidence (15% versrus control, 75%), as assessed 2 m onths after treatment. Histopathological analysis revealed that treated mic e had a lower tumor grade with significant accumulation of inflammatory cel ls in interductal spaces when treated with anti-CTLA-4 and a granulocyte-ma crophage colony-stimulating factor-expressing vaccine, Vaccination of nontr ansgenic mice with this regimen resulted in marked prostatitis accompanied by destruction of epithelium, indicating that the immune response was, at f east in part, directed against normal prostate antigens, These findings dem onstrate that this combinatorial treatment can elicit a potent antiprostate response and suggest potential of this approach for treatment of prostate cancer.