Introduction: Prostate cancer is the most commonly diagnosed cancer in Slovenia and the second most common cause of death due to cancer. About one-third of castrated patients develop incurable, castration-resistant prostate cancer (CRPC). In the last decade, new strategies for treating and controlling the disease have been on the rise, slowing its progression and spread and prolonging survival while maintaining the quality of life. These include immunotherapy.
Aim: In the development of carcinogenesis, cancer cells develop a number of mechanisms that allow cancer cells to survive, proliferate and metastasize. This is also the case with CRPC, so immunotherapy has great potential. One of the immunotherapy strategies we investigated is dendritic cell-based vaccines. We used an advanced autologous cell vaccine with immunohybridomas (aHyC), which was developed in the Republic of Slovenia. We evaluated the safety of a new therapeutic approach and examined the effects of aHyC on the course of CRPC disease by monitoring various clinical parameters. We hypothesized that personalized immunotherapy would be safe, free of serious adverse events, and would not adversely affect the survival of patients with CRPC who had not yet received standard therapy.
Methods: A randomized, double-blind, placebo-controlled, cross-over, phase I/II clinical trial included 22 asymptomatic/minimally symptomatic patients with CRPC. An autologous immunohybridoma cell-based vaccine (aHyC) was prepared by electrofusion of the patient's own dendritic and tumor cells and applied back to the patients, subcutaneously. Patients were randomly divided into 2 blinded groups; the aHyC group (12 patients) who received aHyC and the placebo group (control) who did not receive aHyC (10 patients). Seven weeks after the last dose, a crossover occurred: aHyC group received placebo and placebo group received aHyC in the same regimen. Patients received aHyC four times at three-week intervals. The success of the treatment was evaluated by measuring clinical, imaging, laboratory and immune parameters and by monitoring the quality of life. Survival analysis and identification of prognostic factors were performed.
Results: Only a few mild adverse events were detected in both groups of patients in the study; in 42 % of patients in the aHyC group and in 38 % of patients in the placebo group (z-test, p = 0.85). The quality of life did not change with immunotherapy, as assessed by the sum of the EORTC QLQ-C30 questionnaire scores, which was 64.0 ± 3.7 before aHyC administration and 65.5 ± 4.5 after (p = 0.67). No effects on imaging and on most laboratory parameters were detected. In the aHyC group, a significant decrease in bone alkaline phosphatase and osteocalcin was observed after treatment (p <0.05, p <0.01) compared to pre-treatment values. The median overall survival of all patients receiving aHyC (n = 19) was 58.8 months. We found that there was no statistically significant association between the number of living cells in the vaccine and survival (correlation coefficient, r = -0.14, p = 0.56) as well as the time to the next standard therapy (r = 0.36, p = 0.13).
Conclusion: The results contribute to the development of science in the field of uro-oncology and immunology and provide a better understanding of the course of CRPC disease. Immunotherapy with aHyC shows the first safety signals and has no effect on quality of life.
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