This study presents the outcomes of a Phase I/II clinical trial that examined the safety and effectiveness of using autologous mature dendritic cells (DCs) pulsed with killed LNCaP prostate cancer cells (DCVAC/PCa) in patients with metastatic CRP (mCRPC) who were eligible for docetaxel. The primary objective was to ensure safety, while the secondary objective was to examine the immunological responses. Additionally, overall survival (OS) was compared to the projected OS using the Halabi and MSKCC nomograms as part of the safety review. This innovative treatment approach provides promising results for patients with mCRPC, and may offer new possibilities for improved quality of life and extended survival.
Summary data for 25 individuals is included in this report, comprising 15 patients from a single-institution, single-arm, open-label phase I/II clinical study and 10 patients from a previous patient’s named program (approved by University Hospital Motol IRB).
DNA and RNA preparation
Tumor tissues were obtained by fiber bronchoscopy biopsy, supraclavicular metastatic lymph node resection, fine needle aspiration of metastatic lumbar lesion and fine needle aspiration of lung tumor lesions and stored with 1 ml of RNA later (Thermo Fisher, #AM7020). Blood was collected and mixed with an EDTA- based anticoagulant. DNA and RNA were extracted from the same tumor tissue with the All Prep DNA/RNA Mini Kit, and DNA from EDTA-anti coagulated peripheral blood was extracted with the QIAamp DNA Blood Mini Kit. Quality of DNA/ RNA was evaluated by 2100 Bioanalyzer. Trio samples (two DNA samples from tumor and blood, and one RNA sample from only the tumor) for each patient were prepared for the subsequent sequencing process.
Treatment consisted of initial 7 days administration of metronomic cyclophosphamide 50 mg p.o. DCVAC/PCa treatment consisted of a median twelve doses of 1 × 107 dendritic cells per dose injected s.c. (Aldara creme was applied at the site of injection) during a one-year period. The initial 2 doses of DCVAC/PCa were administered at a 2-week interval, followed by the administration of docetaxel (75 mg/m2) and prednisone (5 mg twice daily) given every 3 weeks until toxicity or intolerance was observed. The DCVAC/PCa was then injected every 6 weeks up to the maximum number of doses manufactured from one leukapheresis.
No serious DCVAC/PCa-related adverse events have been reported. The median OS was 19 months, whereas the predicted median OS was 11.8 months with the Halabi nomogram and 13 months with the MSKCC nomogram. Kaplan-Meier analyses showed that patients had a lower risk of death compared with both MSKCC (Hazard Ratio 0.26, 95% CI: 0.13–0.51) and Halabi (Hazard Ratio 0.33, 95% CI: 0.17–0.63)
predictions. We observed a significant decrease in Tregs in the peripheral blood. The long-term administration of DCVAC/PCa led to the induction and maintenance of PSA specific T cells. We did not identify any immunological parameter that significantly correlated with better OS.
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