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

被引：64

作者：

Angelot-Delettre, Fanny ^{[1
,2
,3
,4
]}

Roggy, Anne ^{[1
,2
,3
,4
]}

Frankel, Arthur E. ^{[5
]}

Lamarthee, Baptiste ^{[1
,2
,3
,4
]}

Seilles, Estelle ^{[1
,2
,3
,4
]}

Biichle, Sabeha ^{[1
,2
,3
,4
]}

Royer, Bernard ^{[1
,2
,3
,4
,6
]}

Deconinck, Eric ^{[1
,2
,3
,4
,6
]}

Rowinsky, Eric K. ^{[7
]}

Brooks, Christopher ^{[7
]}

Bardet, Valerie ^{[8
]}

Benet, Blandine ^{[9
]}

Bennani, Hind ^{[10
]}

Benseddik, Zehaira ^{[11
]}

Debliquis, Agathe ^{[12
]}

Lusina, Daniel ^{[13
]}

Roussel, Mikael ^{[14
]}

Solly, Francoise ^{[15
]}

Ticchioni, Michel ^{[16
]}

Saas, Philippe ^{[1
,2
,3
,4
,17
]}

Garnache-Ottou, Francine ^{[1
,2
,3
,4
]}

机构：

[1] INSERM UMR1098, F-25020 Besancon, France

[2] Univ Bourgogne Franche Comte, SFR FED4234, F-25000 Besancon, France

[3] EFS Bourgogne Franche Comte, F-25020 Besancon, France

[4] LabEX LipSTIC, ANR LABX 0021 11, F-25020 Besancon, France

[5] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA

[6] CHU Besancon, Hematol, F-25030 Besancon, France

[7] Stemline Therapeut Inc, New York, NY USA

[8] Hop Cochin, APHP, F-75674 Paris, France

[9] CHR Metz Thionville, Thionville, France

[10] Hop Rene Huguenin, Inst Curie, St Cloud, France

[11] CH Chartres, Le Coudray, France

[12] CH Mulhouse, Mulhouse, France

[13] APHP Hop Avicenne, Paris, France

[14] CHU Rennes, Rennes, France

[15] CHU St Etienne, St Etienne, France

[16] Univ Nice Sophia Antipolis, F-06189 Nice, France

[17] CHU Besancon, CIC1431, FHU INCREASE, F-25030 Besancon, France

来源：

HAEMATOLOGICA | 2015年 / 100卷 / 02期

关键词：

TOXIN-INTERLEUKIN-3 FUSION PROTEIN; ACUTE MYELOID-LEUKEMIA; COMPLETE REMISSION; FLOW-CYTOMETRY; TRANSPLANTATION; CYTOTOXICITY; METHOTREXATE; EXPRESSION; LYMPHOMAS; AFFINITY;

D O I：

10.3324/haematol.2014.111740

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 a chain (IL3-R alpha or CD 123), 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 CEN2.2) 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.

引用

页码：223 / 230

页数：8

共 42 条

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