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Dendritic cell vaccination in combination with docetaxel for patients with metastatic castration-resistant prostate cancer: A randomized phase II study

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BACKGROUND AIMS: We investigated whether the addition of an autologous dendritic cell-based cancer vaccine (DCvac) induces an immune response in patients with metastatic castration-resistant prostate cancer treated with docetaxel.

METHODS: Forty-three patients were randomized 1:1 to receive up to 10 cycles of docetaxel alone, 75 mg/m2 every 3 weeks or in combination with DCvac. Monocytes were harvested following a leukapheresis procedure, matured ex vivo and subsequently transfected with messenger RNA encoding multiple tumor-associated antigens (TAAs). DCvac was administered intradermally twice through treatment cycles 1-4 and once through treatment cycles 5-10. Immune cell composition and antigen-specific responses were analyzed using flow cytometry, ELISpot and delayed type hypersensitivity (DTH) tests. Toxicity was graded according to Common Terminology Criteria for Adverse Events version 3.0. Progression-free survival (PFS) and disease-specific survival (DSS) was calculated using the Kaplan-Meier method.

RESULTS: Prostate-specific antigen responses were similar in patients treated with docetaxel alone and combination therapy (58% versus 38%; P = 0.21). PFS and DSS were comparable: 5.5 versus 5.7 months (P = 0.62, log rank) and 21.9 versus 25.1 months (P = 0.60, log rank). Nine (50%) and 14 (78%) patients treated with docetaxel and DCvac had a TAA-specific or vaccine-specific immune response in the ELISpot and DTH analysis, respectively. Vaccine induced toxicity was limited to local reactions. Decline in myeloid-derived suppressor cells at the third treatment cycle was found to be an independent predictor of DSS.

CONCLUSIONS: The addition of DCvac was safe. Immune responses were detected in approximately half of the patients investigated.

Original languageEnglish
JournalCytotherapy
Volume19
Issue number4
Pages (from-to)500-513
Number of pages14
ISSN1465-3249
DOIs
Publication statusPublished - Apr 2017

    Research areas

  • Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Cancer Vaccines, Combined Modality Therapy, Dendritic Cells, Disease-Free Survival, Humans, Immunotherapy, Adoptive, Male, Middle Aged, Neoplasm Metastasis, Prostatic Neoplasms, Castration-Resistant, Taxoids, Transplantation, Autologous, Treatment Outcome, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't

ID: 52211061