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

Fiche publication


Date publication

février 2015

Auteurs

Membres identifiés du Cancéropôle Est :
Pr DECONINCK Eric, Pr GARNACHE-OTTOU Francine, Dr ROYER Bernard, Dr DEBLIQUIS Agathe, Dr ANGELOT-DELETTRE Fanny


Tous les auteurs :
Angelot-Delettre F, Roggy A, Frankel AE, Lamarthee B, Seilles E, Biichle S, Royer B, Deconinck E, Rowinsky EK, Brooks C, Bardet V, Benet B, Bennani H, Benseddik Z, Debliquis A, Lusina D, Roussel M, Solly F, Ticchioni M, Saas P, Garnache-Ottou F

Résumé

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 alpha chain (IL3-Ralpha 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

Référence

Haematologica. 2015 Feb;100(2):223-30