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, Anne Roggy, Arthur E. Frankel, Baptiste Lamarthee, Estelle Seilles, Sabeha Biichle, Bernard Royer, Eric Deconinck, Eric K. Rowinsky, Christopher Brooks, Valerie Bardet, Blandine Benet, Hind Bennani, Zehaira Benseddik, Agathe Debliquis, Daniel Lusina, Mikael Roussel, Françoise Solly, Michel Ticchioni, Philippe SaasFrancine Garnache-Ottou

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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 inter-leukin-3 receptor a chain (IL3-Ra 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.

Original languageEnglish (US)
Pages (from-to)223-230
Number of pages8
JournalHaematologica
Volume100
Issue number2
DOIs
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Hematology

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    Angelot-Delettre, F., Roggy, A., Frankel, A. E., Lamarthee, B., Seilles, E., Biichle, S., Royer, B., Deconinck, E., Rowinsky, E. K., Brooks, C., Bardet, V., Benet, B., Bennani, H., Benseddik, Z., Debliquis, A., Lusina, D., Roussel, M., Solly, F., Ticchioni, M., ... Garnache-Ottou, F. (2015). In vivo and in vitro sensitivity of blastic plasmacytoid dendritic cell neoplasm to sl-401, an interleukin-3 receptor targeted biologic agent. Haematologica, 100(2), 223-230. https://doi.org/10.3324/haematol.2014.111740