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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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@article{e3c882c3c12948409323ab559fa573ac,
title = "Dendritic cell vaccination in combination with docetaxel for patients with metastatic castration-resistant prostate cancer: A randomized phase II study",
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 = "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",
author = "Per Kongsted and Borch, {Troels Holz} and Eva Ellebaek and Iversen, {Trine Zeeberg} and Rikke Andersen and {\"O}zcan Met and Morten Hansen and Henriette Lindberg and Lisa Sengel{\o}v and Svane, {Inge Marie}",
note = "Copyright {\textcopyright} 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.",
year = "2017",
month = apr,
doi = "10.1016/j.jcyt.2017.01.007",
language = "English",
volume = "19",
pages = "500--513",
journal = "Cytotherapy",
issn = "1465-3249",
publisher = "Informa Healthcare",
number = "4",

}

RIS

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

N1 - Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

PY - 2017/4

Y1 - 2017/4

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 - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Cancer Vaccines

KW - Combined Modality Therapy

KW - Dendritic Cells

KW - Disease-Free Survival

KW - Humans

KW - Immunotherapy, Adoptive

KW - Male

KW - Middle Aged

KW - Neoplasm Metastasis

KW - Prostatic Neoplasms, Castration-Resistant

KW - Taxoids

KW - Transplantation, Autologous

KW - Treatment Outcome

KW - Clinical Trial, Phase II

KW - Journal Article

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.jcyt.2017.01.007

DO - 10.1016/j.jcyt.2017.01.007

M3 - Journal article

C2 - 28215654

VL - 19

SP - 500

EP - 513

JO - Cytotherapy

JF - Cytotherapy

SN - 1465-3249

IS - 4

ER -

ID: 52211061