Dendritic cell vaccination in combination with docetaxel for patients with metastatic castration-resistant prostate cancer: A randomized phase II study
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Dendritic cell vaccination in combination with docetaxel for patients with metastatic castration-resistant prostate cancer : A randomized phase II study. / Kongsted, Per; Borch, Troels Holz; Ellebaek, Eva; Iversen, Trine Zeeberg; Andersen, Rikke; Met, Özcan; Hansen, Morten; Lindberg, Henriette; Sengeløv, Lisa; Svane, Inge Marie.
I: Cytotherapy, Bind 19, Nr. 4, 01.04.2017, s. 500-513.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Dendritic cell vaccination in combination with docetaxel for patients with metastatic castration-resistant prostate cancer
T2 - A randomized phase II study
AU - Kongsted, Per
AU - Borch, Troels Holz
AU - Ellebaek, Eva
AU - Iversen, Trine Zeeberg
AU - Andersen, Rikke
AU - Met, Özcan
AU - Hansen, Morten
AU - Lindberg, Henriette
AU - Sengeløv, Lisa
AU - Svane, Inge Marie
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
KW - chemotherapy
KW - dendritic cells
KW - immunotherapy
KW - mCRPC
KW - prostate cancer
U2 - 10.1016/j.jcyt.2017.01.007
DO - 10.1016/j.jcyt.2017.01.007
M3 - Journal article
C2 - 28215654
AN - SCOPUS:85012914647
VL - 19
SP - 500
EP - 513
JO - Cytotherapy
JF - Cytotherapy
SN - 1465-3249
IS - 4
ER -
ID: 176375517