A phase I prospective, non-randomized trial of autologous dendritic cell-based cryoimmunotherapy in patients with metastatic castration-resistant prostate cancer
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A phase I prospective, non-randomized trial of autologous dendritic cell-based cryoimmunotherapy in patients with metastatic castration-resistant prostate cancer. / Thomsen, Liv Cecilie Vestrheim; Honoré, Alfred; Reisæter, Lars Anders Rokne; Almås, Bjarte; Børretzen, Astrid; Helle, Svein Inge; Førde, Kristina; Kristoffersen, Einar Klæboe; Kaada, Silje Helland; Melve, Guro Kristin; Haslerud, Torjan Magne; Biermann, Martin; Bigalke, Iris; Kvalheim, Gunnar; Azeem, Waqas; Olsen, Jan Roger; Gabriel, Benjamin; Knappskog, Stian; Halvorsen, Ole Johan; Akslen, Lars Andreas; Bahn, Duke; Pantel, Klaus; Riethdorf, Sabine; Ragde, Haakon; Gjertsen, Bjørn Tore; Øyan, Anne Margrete; Kalland, Karl-Henning; Beisland, Christian.
in: CANCER IMMUNOL IMMUN, Jahrgang 72, Nr. 7, 07.2023, S. 2357-2373.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - A phase I prospective, non-randomized trial of autologous dendritic cell-based cryoimmunotherapy in patients with metastatic castration-resistant prostate cancer
AU - Thomsen, Liv Cecilie Vestrheim
AU - Honoré, Alfred
AU - Reisæter, Lars Anders Rokne
AU - Almås, Bjarte
AU - Børretzen, Astrid
AU - Helle, Svein Inge
AU - Førde, Kristina
AU - Kristoffersen, Einar Klæboe
AU - Kaada, Silje Helland
AU - Melve, Guro Kristin
AU - Haslerud, Torjan Magne
AU - Biermann, Martin
AU - Bigalke, Iris
AU - Kvalheim, Gunnar
AU - Azeem, Waqas
AU - Olsen, Jan Roger
AU - Gabriel, Benjamin
AU - Knappskog, Stian
AU - Halvorsen, Ole Johan
AU - Akslen, Lars Andreas
AU - Bahn, Duke
AU - Pantel, Klaus
AU - Riethdorf, Sabine
AU - Ragde, Haakon
AU - Gjertsen, Bjørn Tore
AU - Øyan, Anne Margrete
AU - Kalland, Karl-Henning
AU - Beisland, Christian
N1 - © 2023. The Author(s).
PY - 2023/7
Y1 - 2023/7
N2 - Metastatic castration-resistant prostate cancer (mCRPC) is an immunologically cold disease with dismal outcomes. Cryoablation destroys cancer tissue, releases tumor-associated antigens and creates a pro-inflammatory microenvironment, while dendritic cells (DCs) activate immune responses through processing of antigens. Immunotherapy combinations could enhance the anti-tumor efficacy. This open-label, single-arm, single-center phase I trial determined the safety and tolerability of combining cryoablation and autologous immature DC, without and with checkpoint inhibitors. Immune responses and clinical outcomes were evaluated. Patients with mCRPC, confirmed metastases and intact prostate gland were included. The first participants underwent prostate cryoablation with intratumoral injection of autologous DCs in a 3 + 3 design. In the second part, patients received cryoablation, the highest acceptable DC dose, and checkpoint inhibition with either ipilimumab or pembrolizumab. Sequentially collected information on adverse events, quality of life, blood values and images were analyzed by standard descriptive statistics. Neither dose-limiting toxicities nor adverse events > grade 3 were observed in the 18 participants. Results indicate antitumor activity through altered T cell receptor repertoires, and 33% durable (> 46 weeks) clinical benefit with median 40.7 months overall survival. Post-treatment pain and fatigue were associated with circulating tumor cell (CTC) presence at inclusion, while CTC responses correlated with clinical outcomes. This trial demonstrates that cryoimmunotherapy in mCRPC is safe and well tolerated, also for the highest DC dose (2.0 × 108) combined with checkpoint inhibitors. Further studies focusing on the biologic indications of antitumor activity and immune system activation could be considered through a phase II trial focusing on treatment responses and immunologic biomarkers.
AB - Metastatic castration-resistant prostate cancer (mCRPC) is an immunologically cold disease with dismal outcomes. Cryoablation destroys cancer tissue, releases tumor-associated antigens and creates a pro-inflammatory microenvironment, while dendritic cells (DCs) activate immune responses through processing of antigens. Immunotherapy combinations could enhance the anti-tumor efficacy. This open-label, single-arm, single-center phase I trial determined the safety and tolerability of combining cryoablation and autologous immature DC, without and with checkpoint inhibitors. Immune responses and clinical outcomes were evaluated. Patients with mCRPC, confirmed metastases and intact prostate gland were included. The first participants underwent prostate cryoablation with intratumoral injection of autologous DCs in a 3 + 3 design. In the second part, patients received cryoablation, the highest acceptable DC dose, and checkpoint inhibition with either ipilimumab or pembrolizumab. Sequentially collected information on adverse events, quality of life, blood values and images were analyzed by standard descriptive statistics. Neither dose-limiting toxicities nor adverse events > grade 3 were observed in the 18 participants. Results indicate antitumor activity through altered T cell receptor repertoires, and 33% durable (> 46 weeks) clinical benefit with median 40.7 months overall survival. Post-treatment pain and fatigue were associated with circulating tumor cell (CTC) presence at inclusion, while CTC responses correlated with clinical outcomes. This trial demonstrates that cryoimmunotherapy in mCRPC is safe and well tolerated, also for the highest DC dose (2.0 × 108) combined with checkpoint inhibitors. Further studies focusing on the biologic indications of antitumor activity and immune system activation could be considered through a phase II trial focusing on treatment responses and immunologic biomarkers.
KW - Humans
KW - Male
KW - Dendritic Cells
KW - Ipilimumab/therapeutic use
KW - Prospective Studies
KW - Prostatic Neoplasms, Castration-Resistant/therapy
KW - Quality of Life
KW - Tumor Microenvironment
U2 - 10.1007/s00262-023-03421-7
DO - 10.1007/s00262-023-03421-7
M3 - SCORING: Journal article
C2 - 36939854
VL - 72
SP - 2357
EP - 2373
JO - CANCER IMMUNOL IMMUN
JF - CANCER IMMUNOL IMMUN
SN - 0340-7004
IS - 7
ER -