POUŽITÍ DENDRITICKÝCH BUNĚK V LÉČBĚ KARCINOMU PROSTATY PROSTATE CANCER IMMUNOTHERAPY BY DENDRITIC CELLS

In Europe, prostate cancer is the most frequent solid neoplasm in men, with an incidence rate of 214 cases per 1000 men. Despite high currative rate of surgery or radiotherapy in localised disease, substantial proportion of patients progress after primary treatment to metastatic disease. The hormonal therapy is the only treatment of systemic disease. Ultimate treatment option in the stage of castrate- -resistant prostate cancer (CRCP) is chemotherapy which increases median survival by aprox. 3 months. Recently, FDA approved first immunotherapy product (Provenge), that showed increased median survival by 4,5 months in minimally symptomatic CRCP patients. Any treatment which may prevent biochemical recurrence in early stages, stabilizes the PSA-progression after biochemical relapse and increases time to hormonal failure or stabilizes the CRCP stage, may have important impact on overal survival and quality of life.

Dendritic-cell based vaccine against prostate cancer (DCVAC/Pca) was developed in our department. Proof-of-principle was tested in preclinical in vitro cross-presentation studies which showed that LNCaP tumour-cell-line pulsed and poly-IC maturated DCs are able to induce tumour specific CD4 and CD8 T cells producing IFN-γ. Pharmacokinetics of DCVAC was done in humans using DCs labelled with Indium (111In)-oxine. Over the period of 48 hours, fused, SPECT/low-dose CT images targeted to the application site were performed. This method showed that labelled DCs migrated into the regional lymph nodes, the site of immune response.

In 2008, first in human experience of DCVAC/PCa occurred. By end of 2011, 290 doses of ACI were administered to 28 patients in two clinical trials. No serious adverse side effects were observed. In the first trial, prolongation of PSA doubling time (calculated before and during the immunotherapy) was observed in patients with raising PSA after radical prostatectomy. Significant slow down of PSA progression was detected in 85 % of patients enrolled. Second trial in patients with castrate-resistant prostate cancer is based on the principle of „chemoimmunotherapy” combining the active cancer immunotherapy with chemotherapy by docetaxel. Combined chemoimmunotherapy led to stabilization of the disease and longer than expected (according to Halabi nomograms) survival.

e-mail: jirina.bartunkova@lfmotol.cuni.cz