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

Fanny Angelot-Delettre 1 Anne Roggy 1 Arthur Frankel 2 Baptiste Lamarthee 1 Estelle Seilles 1 Sabeha Biichle 1 Bernard Royer 1 Eric Deconinck 3 Eric Rowinsky 4 Christopher Brooks 4 Valerie Bardet 5 Blandine Benet 6 Hind Bennani 7 Zehaira Benseddik 8 Agathe Debliquis 9 Daniel Lusina 10 Mikael Roussel 11 Françoise Solly 12 Michel Ticchioni 13 Philippe Saas 1 Francine Garnache-Ottou 1, *
* Corresponding author
1 HOTE GREFFON - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
2 University of Texas Southwestern Medical Center [Dallas]
3 Laboratoire d'Hématologie
4 Research and Development
5 Laboratoire d'Hématologie Biologique
6 Laboratoire de Biologie
7 Biologie Médicale et Physiologie
8 Laboratoire de Biologie Médicale
9 Laboratoire d'hématologie
10 Service d'hématologie biologique [Avicenne]
11 Service d'Anatomie et Cytologie Pathologique B
12 Laboratoire de Biologie - Pathologie
13 Département d'Immunologie
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.
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https://www.hal.inserm.fr/inserm-01146053
Contributor : Philippe Saas <>
Submitted on : Monday, April 27, 2015 - 3:44:07 PM
Last modification on : Tuesday, September 22, 2020 - 3:57:46 AM
Long-term archiving on: : Wednesday, April 19, 2017 - 7:48:21 AM

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  • HAL Id : inserm-01146053, version 1
  • PUBMED : 25381130

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UNIV-FCOMTE | UMR645 | FNCLCC | CURIE | UNIV-PARIS5 | UNIV-RENNES1 | UNIV-PARIS13 | USPC | UNIV-RENNES | PSL

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Fanny Angelot-Delettre, Anne Roggy, Arthur Frankel, Baptiste Lamarthee, Estelle Seilles, et al.. In vivo and in vitro sensitivity of blastic plasmacytoid dendritic cell neoplasm to SL-401, an interleukin-3 receptor targeted biologic agent.. Haematologica, Ferrata Storti Foundation, 2015, 100 (2), pp.223-30. ⟨inserm-01146053⟩

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