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Haematologica. 2015 Feb;100(2):223-30. doi: 10.3324/haematol.2014.111740. Epub 2014 Nov 7.

In vivo and in vitro sensitivity of blastic plasmacytoid dendritic cell neoplasm to SL-401, an interleukin-3 receptor targeted biologic agent.

Author information

1
INSERM UMR1098, F25020 Besançon Cedex, France Université de Bourgogne Franche-Comté, SFR FED4234, F25000 Besançon Cedex, France EFS Bourgogne Franche-Comté, F25020 Besançon Cedex, France LabEX LipSTIC, ANR-11-LABX-0021, F25020 Besançon Cedex, France.
2
Southwestern Medical Center, Dallas, TX, USA.
3
INSERM UMR1098, F25020 Besançon Cedex, France Université de Bourgogne Franche-Comté, SFR FED4234, F25000 Besançon Cedex, France EFS Bourgogne Franche-Comté, F25020 Besançon Cedex, France LabEX LipSTIC, ANR-11-LABX-0021, F25020 Besançon Cedex, France CHU Besançon, Hematology, France.
4
Stemline Therapeutics, Inc, 750 Lexington Avenue, 11th Floor, New York, USA.
5
APHP, Hopital Cochin, Paris, France.
6
CHR Metz Thionville, France.
7
Institut Curie, Hopital René Huguenin, Saint Cloud, France.
8
CH Chartres, Le Coudray, France.
9
CH Mulhouse, France.
10
APHP Hopital Avicenne, Paris, France.
11
CHU Rennes, Rennes, France.
12
CHU St Etienne, Saint Etienne, France.
13
Université de Nice-Sophia Antipolis, Nice, France.
14
INSERM UMR1098, F25020 Besançon Cedex, France Université de Bourgogne Franche-Comté, SFR FED4234, F25000 Besançon Cedex, France EFS Bourgogne Franche-Comté, F25020 Besançon Cedex, France LabEX LipSTIC, ANR-11-LABX-0021, F25020 Besançon Cedex, France CHU Besançon, CIC1431, FHU INCREASE, Besançon, France.
15
INSERM UMR1098, F25020 Besançon Cedex, France Université de Bourgogne Franche-Comté, SFR FED4234, F25000 Besançon Cedex, France EFS Bourgogne Franche-Comté, F25020 Besançon Cedex, France LabEX LipSTIC, ANR-11-LABX-0021, F25020 Besançon Cedex, France francine.garnache@efs.sante.fr.

Abstract

Blastic plasmacytoid dendritic cell neoplasm is an aggressive malignancy derived from plasmacytoid dendritic cells. There is currently no accepted standard of care for treating this neoplasm, and therapeutic strategies have never been prospectively evaluated. Since blastic plasmacytoid dendritic cell neoplasm cells express high levels of interleukin-3 receptor α chain (IL3-Rα or CD123), antitumor effects of the interleukin-3 receptor-targeted drug SL-401 against blastic plasmacytoid dendritic cell neoplasm were evaluated in vitro and in vivo. The cytotoxicity of SL-401 was assessed in patient-derived blastic plasmacytoid dendritic cell neoplasm cell lines (CAL-1 and GEN2.2) and in primary blastic plasmacytoid dendritic cell neoplasm cells isolated from 12 patients using flow cytometry and an in vitro cytotoxicity assay. The cytotoxic effects of SL-401 were compared to those of several relevant cytotoxic agents. SL-401 exhibited a robust cytotoxicity against blastic plasmacytoid dendritic cell neoplasm cells in a dose-dependent manner. Additionally, the cytotoxic effects of SL-401 were observed at substantially lower concentrations than those achieved in clinical trials to date. Survival of mice inoculated with a blastic plasmacytoid dendritic cell neoplasm cell line and treated with a single cycle of SL-401 was significantly longer than that of untreated controls (median survival, 58 versus 17 days, P<0.001). These findings indicate that blastic plasmacytoid dendritic cell neoplasm cells are highly sensitive to SL-401, and support further evaluation of SL-401 in patients suffering from blastic plasmacytoid dendritic cell neoplasm.

PMID:
25381130
PMCID:
PMC4803130
DOI:
10.3324/haematol.2014.111740
[Indexed for MEDLINE]
Free PMC Article

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