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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.
- Source :
-
Haematologica [Haematologica] 2015 Feb; Vol. 100 (2), pp. 223-30. Date of Electronic Publication: 2014 Nov 07. - Publication Year :
- 2015
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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 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.<br /> (Copyright© Ferrata Storti Foundation.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Animals
Apoptosis
Biomarkers, Tumor genetics
Blotting, Western
Cell Proliferation
Dendritic Cells metabolism
Female
Flow Cytometry
Hematologic Neoplasms metabolism
Hematologic Neoplasms therapy
Humans
In Vitro Techniques
Interleukin-3 Receptor alpha Subunit genetics
Interleukin-3 Receptor alpha Subunit metabolism
Male
Mice
Mice, Inbred NOD
Mice, SCID
Middle Aged
Myeloproliferative Disorders metabolism
Myeloproliferative Disorders therapy
Plasmacytoma metabolism
Plasmacytoma therapy
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Biomarkers, Tumor metabolism
Dendritic Cells pathology
Hematologic Neoplasms pathology
Interleukin-3 Receptor alpha Subunit antagonists & inhibitors
Myeloproliferative Disorders pathology
Plasmacytoma pathology
Recombinant Fusion Proteins therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1592-8721
- Volume :
- 100
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 25381130
- Full Text :
- https://doi.org/10.3324/haematol.2014.111740