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Cytotherapy. 2017 Apr;19(4):500-513. doi: 10.1016/j.jcyt.2017.01.007. Epub 2017 Feb 15.

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

Author information

1
Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark; Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
2
Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
3
Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
4
Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark; Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Electronic address: inge.marie.svane@regionh.dk.

Abstract

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.

KEYWORDS:

chemotherapy; dendritic cells; immunotherapy; mCRPC; prostate cancer

PMID:
28215654
DOI:
10.1016/j.jcyt.2017.01.007
[Indexed for MEDLINE]

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