In vivo and in vitro sensitivity of blastic plasmacytoid dendritic cell neoplasm to SL-401, an interleukin-3 receptor targeted biologic agent.
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.
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.
Fanny
F
Angelot-Delettre
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.
Anne
A
Roggy
Southwestern Medical Center, Dallas, TX, USA.
Arthur E
AE
Frankel
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.
Baptiste
B
Lamarthee
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.
Estelle
E
Seilles
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.
Sabeha
S
Biichle
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.
Bernard
B
Royer
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.
Eric
E
Deconinck
Stemline Therapeutics, Inc, 750 Lexington Avenue, 11th Floor, New York, USA.
Eric K
EK
Rowinsky
Stemline Therapeutics, Inc, 750 Lexington Avenue, 11th Floor, New York, USA.
Christopher
C
Brooks
APHP, Hopital Cochin, Paris, France.
Valerie
V
Bardet
CHR Metz Thionville, France.
Blandine
B
Benet
Institut Curie, Hopital René Huguenin, Saint Cloud, France.
Hind
H
Bennani
CH Chartres, Le Coudray, France.
Zehaira
Z
Benseddik
CH Mulhouse, France.
Agathe
A
Debliquis
APHP Hopital Avicenne, Paris, France.
Daniel
D
Lusina
CHU Rennes, Rennes, France.
Mikael
M
Roussel
CHU St Etienne, Saint Etienne, France.
Françoise
F
Solly
Université de Nice-Sophia Antipolis, Nice, France.
Michel
M
Ticchioni
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.
Philippe
P
Saas
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.
Francine
F
Garnache-Ottou
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D019337:Hematologic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D006801:Humans; D066298:In Vitro Techniques; D053650:Interleukin-3 Receptor alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D010954:Plasmacytoma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D011993:Recombinant Fusion Proteins; C000592123:tagraxofusp