889 ANTIGEN-SPECIFIC T CELL RESPONSES AGAINST TUMOR-ANTIGENS ARE CONTROLLED BY REGULATORY T CELLS IN PROSTATE CANCER PATIENTS

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THE JOURNAL OF UROLOGY姞

gr/cm2 in Group 2 (p⬎0,05). In Group 1, 10yHFR decreased from 3,29% to 2,92% in FRAX nomogram (p⬎0,05) and increased from 9,65% to 9,91% in Garvan nomogram (p⬎0,05). In Group 2, 10yHFR increased from 3,36% to 3,62% in FRAX nomogram (p⬎0,05) and from 8,79% to 10,85% in Garvan nomograms (p⬎0,05). In Group 1, 10yMOFR decreased from 6,04% to 5,63% in FRAXnomogram (p⬎0,05) and increased from 22,24% to 23,17% in Garvan nomogram (p⬎0,05). In Group 2, 10yMOFR increased from 6,03% to 6,36% in FRAX nomogram (p⬎0,05) and from 16% to 17,72% in Garvan nomogram (p⬎0,05). CONCLUSIONS: Alendronate increases BMD in osteoporotic PCA patients under AS and decrease 10yHFR and 10yMOFR according to FRAX nomogram. The behavior of Garvan nomogram does not correlate with BMD changes and its accuracy to predict 10 years fracture risk seems not appropiate in these patients. Source of Funding: None

889 ANTIGEN-SPECIFIC T CELL RESPONSES AGAINST TUMOR-ANTIGENS ARE CONTROLLED BY REGULATORY T CELLS IN PROSTATE CANCER PATIENTS Boris Hadaschik*, Heidelberg, Germany; Yun Su, Nanjing, China, People’s Republic of; Eva Hadaschik, Markus Hohenfellner, Philipp Beckhove, Heidelberg, Germany INTRODUCTION AND OBJECTIVES: Immunotherapeutic approaches belong to the most promising regimen in an effort to control castration-resistant prostate cancer. Therapeutic cancer vaccines have been investigated intensively, but most vaccine strategies have shown only limited success. This might be explained by suppression of anti-tumor T cell responses by regulatory T cells (Treg). In prostate cancer patients, both increased levels of Treg in the tumor as well as an enhanced functionality of Treg in the peripheral blood have been described. In the current project, we characterized the natural repertoire of tumor antigen-reactive T cells in patients with prostate cancer and analyzed their control by Tregs. METHODS: Peripheral blood samples were collected from 57 patients with histologically confirmed prostate cancer, 8 patients with BPH, and 16 healthy donors. Peripheral blood mononuclear cells (PBMC) were isolated by Ficoll gradient and antigen-specific IFN-␥ secretion of isolated T cells was analyzed by ELISPOT assays. T cell responses before and after Treg-depletion with CD25 magnetic beads were compared. As test tumor antigens, we used a panel of 11 long synthetic peptides derived from 8 different tumor antigens including PSA, PAP3 and PAP5. RESULTS: In prostate cancer patients we observed an effector T cell response rate of 74.5% compared with only 25% in BPH and 31% in healthy donors. Most patients recognized 2–3 different tumor antigens. Looking at various stages of the disease, there was a clear increase in immune responses against prostate-specific antigens from intermediate to high risk tumors and castrationresistant disease. Depletion of Tregs led to a significant increase in effector T cell responses against PSA, PAP3 and PAP5. CONCLUSIONS: Tumor-specific effector T cells were detectable in the majority of prostate cancer patients and especially in men with castration-resistant disease. Since effector T cell responses against prostate-specific antigens strongly increased after Treg depletion, our results indicate that immune modulations such as personalized peptide vaccination could be augmented by prevention of Treg accumulation. Source of Funding: DFG

Vol. 185, No. 4S, Supplement, Monday, May 16, 2011

890 SENSITIVITY FACTORS ANALYSIS ON LOW DOSE KETOCONAZOLE PLUS PREDNISONE EFFECTIVE TREATMENT FOR CASTRATION RESISTANT PROSTATE CANCER Guo-Wen Lin*, Xu-Dong Yao, Ding-Wei Ye, Bo Dai, Yao Zhu, Shanghai, China, People’s Republic of INTRODUCTION AND OBJECTIVES: To explore whether there were some predictors of low dose ketoconazole(LDK) effective treatment for castration resistant prostate cancer(CRPC). METHODS: 71 patients with CRPC were eligible for this retrospective study. They underwent previous hormonal therapy failure and 14 patients had been given chemotherapy based on docetaxel. At the baseline, serum PSA, testosterone and hemoglobin were detected. Ketoconazole orally 200mg three times daily as LDK with prednisone 5mg twice a day was performed for these patients. PSA doubling time (PSADT) was applied, which was defined as PSA increase status before LDK therapy. The equation was PSADT⫽ log(2)⫻⌬T/[log(PSAbaseline)-log(PSAfailue)], in which PSAbaseline indicated baseline PSA and PSAfailue was the first value of previous treatment failure, ⌬T was the time interval between them. As response criteria of effective treatment, PSA response rate was defined as the percentage of patients with PSA decline⬎⫽50% compared PSAbaseline. Continuous variables were categorized in analysis by optimal cutoff which provided the greatest prognostic value by P value-based approach. A multivariate model was used to develop a nomogram predicting PSA response. RESULTS: 22 (31.0%) patients were evaluable as PSA responders. Table 1 indicated baseline testosterone and PSADT as sensitivity predictors for LDK effective treatment in logistic regression models. PSA response rate was 55.6%(20/36) and 5.7%(2/35) for patients with baseline testosterone⬎⫽0.1ng/mL and ⬍0.1ng/mL and was 44.8%(13/29) and 21.4%(9/42) for patients with PSADT⬎⫽2.0 month and ⬍2.0 month. The area under the curve (AUC) of receiver operating characteristic for then were 0.791(95% confidence interval[CI] 0.682-0.900) and 0.632(95% CI 0.490-0.774).Figure 1 showed the result of nomogram. CONCLUSIONS: The baseline testosterone⬎⫽0.1ng/mL and PSADT⬎⫽2.0 month may be new predictors for better outcome of LDK therapy for CRPC.