Orphan designation: recombinant human interleukin-3 truncated diphtheria toxin fusion protein, Treatment of blastic plasmacytoid dendritic cell neoplasm

2018 ◽  
Author(s):  
Keyword(s):  
Dendritic Cell ◽  
Fusion Protein ◽  
Diphtheria Toxin ◽  
Plasmacytoid Dendritic Cell ◽  
Orphan Designation ◽  
Interleukin 3 ◽  
Cell Neoplasm ◽  
Protein Treatment

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

Haematologica ◽  
2014 ◽  
Vol 100 (2) ◽  
pp. 223-230 ◽  
Author(s):  
F. Angelot-Delettre ◽  
A. Roggy ◽  
A. E. Frankel ◽  
B. Lamarthee ◽  
E. Seilles ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Biologic Agent ◽  
Interleukin 3 ◽  
In Vitro Sensitivity ◽  
Cell Neoplasm

scholarly journals Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients

Blood ◽  
2014 ◽  
Vol 124 (3) ◽  
pp. 385-392 ◽  
Author(s):  
Arthur E. Frankel ◽  
Jung H. Woo ◽  
Chul Ahn ◽  
Naveen Pemmaraju ◽  
Bruno C. Medeiros ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Dendritic Cell ◽  
Plasmacytoid Dendritic Cell ◽  
High Rate ◽  
Interleukin 3 ◽  
Key Points ◽  
Cell Neoplasm

Key PointsSL-401 was well tolerated, and a single course of treatment produced a high rate of objective responses in BPDCN patients.

Clinical and preclinical activity of SL-401, a targeted therapy directed to the interleukin-3 receptor on cancer stem cells and tumor bulk of hematologic malignancies, against blastic plasmacytoid dendritic cell neoplasm (BPDCN).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS3105-TPS3105
Author(s):  
Arthur E. Frankel ◽  
Jung Hee Woo ◽  
Jeremy Preston Mauldin ◽  
Hetty Eileen Carraway ◽  
Olga Frankfurt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Targeted Therapy ◽  
Dendritic Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Hematologic Malignancies ◽  
Allogeneic Bone ◽  
Pivotal Phase ◽  
Interleukin 3 ◽  
Cell Neoplasm ◽  
Inhibitor Of Protein Synthesis

TPS3105^ Background: Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN), a rare and aggressive dendritic cell-derived hematologic malignancy that typically involves the skin and invariably progresses to a leukemic phase, has a dismal prognosis with a median survival of approximately 14 months. Since BPDCN cells express high levels of the interleukin-3 receptor (IL-3R), SL-401, a novel targeted therapy directed to IL-3R, is being developed to treat BPDCN and other IL-3R-expressing hematologic malignancies. SL-401 is a recombinant biologic comprised of IL-3 conjugated to a truncated diphtheria toxin, a potent inhibitor of protein synthesis (Frankel et al, Prot Eng 13, 575, 2000). SL-401 is cytotoxic in vitro to IL-3R-expressing leukemia blasts (Frankel et al, Leukemia 14, 576, 2000) and inhibits tumor growth in vivo (Black et al, Leukemia 17, 155, 2003). Recently, SL-401 demonstrated ultra-high anti-tumor potency against BPDCN cells in the femtomolar (10-15 M) range (Angelot-Delettre et al, Blood 118 Suppl 2588, 2011). Methods: In a Phase I/II trial of SL-401 in patients with IL-3R-expressing advanced hematologic malignancies, 4 patients with heavily pretreated BPDCN received a single cycle of SL-401 as a 15-minute infusion daily for 5 days. Results: All patients had CD4+/CD56+/CD123+ (IL-3Ralpha) expressing blasts and had failed previous combination chemotherapy regimens and allogeneic bone marrow transplantation. There were no serious adverse events. Three patients treated with SL-401 at 12.5 μg/kg/day (the planned pivotal Phase IIb trial dose) experienced complete responses (CRs). The CRs included disappearance of BPDCN in the skin, bone marrow, peripheral blood, spleen and lymph nodes. CR durations are 5, 3+, and 1+ months to date. Conclusions: Given these robust clinical responses, as well as the mechanistic rationale for SL-401 in BPDCN, additional BPDCN patients are being evaluated in the study and a pivotal Phase IIb multi-cycle trial in this ultra-orphan indication is being planned. Clinical trial information: NCT00397579.

Tagraxofusp and anti-CD123 in blastic plasmacytoid dendritic cell neoplasm: a new hope

2020 ◽  
Vol 111 (5) ◽  
Author(s):  
Delia Cangini ◽  
Paolo Silimbani ◽  
Alessandro Cafaro ◽  
Maria B. Giannini ◽  
Carla Masini ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Cell Neoplasm
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