Background: Effect of cancer immunotherapy at the minimal residual disease stage can be evaluated in patients with the biochemical relapse of the prostate cancer. We performed a Phase I/II clinical trial in patients with the biochemical relapse of the prostate cancer using autologous mature dendritic cells pulsed with killed LNCap prostate cancer cell line, DCVAC/PCa. Methods: Eligible patients had a biochemical relapse of the prostate cancer after primary prostatectomy or after radical prostatectomy and salvage radiotherapy. Absence of hormonal therapy was required. DCVAC/PCa treatment consisted of twelve doses of 1x10⁷dendritic cells injected s.c. Treatment comprised of initial 2 doses in 2 weeks interval and DCVAC/PCa was then administered every four weeks for a total of twelve doses. Patients experiencing significant prolongation/stabilization of PSA-DT were eligible for an additional treatment cycle. Primary goal of the study was to assess safety. Secondary goals were PSA kinetics and presence of tumor specific immunity. Results: Twenty one patients were evaluated after receiving 12 doses of DCVAC/PCa. Administration of DCVAC/PCa did not lead to any significant side effects. Continuous cancer immunotherapy by DCVAC/PCa significantly prolonged the PSA doubling time (PSA-DT) in all treated patients. Median PSA-DT increased from 7,86 months prior to the treatment, to 26,08 months after completing 12 doses of DCVAC/PCa, p<0.001. Eight of 21 patients had stable PSA levels during the treatment duration (PSA-DT>36 months) and PSA-DT remained stable during the additional cycle of the treatment (average PSA-DT of 48,13 months). Long-term administration of DCVAC/PCa led to the induction and maintenance of T cells specific against multiple tumor antigens including PSA, MAGE-A1 and MAGE-A3. Conclusions: This study indicates that the cancer immunotherapy with DCVAC/PCa represents a promising approach for prostate cancer patients with biochemical relapse. This study supports the use of immunotherapy early in the course of the disease, provided that relevant surrogate endpoints predictive of improved prognosis of early stage patients will be identified. Clinical trial information: 2009-017259-91.