Synthetic high-density lipoproteins as targeted monotherapy for chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) remains incurable despite the introduction of new drugs. Therapies targeting receptors and pathways active specifically in malignant B cells might provide better treatment options. For instance, in B cell lymphoma, our group has previously shown that scavenger rece...

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Bibliographic Details
Published in:Oncotarget 2017-02, Vol.8 (7), p.11219-11227
Main Authors: McMahon, Kaylin M, Scielzo, Cristina, Angeloni, Nicholas L, Deiss-Yehiely, Elad, Scarfo, Lydia, Ranghetti, Pamela, Ma, Shuo, Kaplan, Jason, Barbaglio, Federica, Gordon, Leo I, Giles, Francis J, Thaxton, C Shad, Ghia, Paolo
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Binding, Competitive
Blotting, Western
CD36 Antigens - antagonists & inhibitors
CD36 Antigens - metabolism
Cells, Cultured
Female
Flow Cytometry
Humans
Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy
Leukemia, Lymphocytic, Chronic, B-Cell - metabolism
Leukemia, Lymphocytic, Chronic, B-Cell - pathology
Leukocytes, Mononuclear - cytology
Leukocytes, Mononuclear - drug effects
Leukocytes, Mononuclear - metabolism
Lipoproteins, HDL - chemical synthesis
Lipoproteins, HDL - metabolism
Lipoproteins, HDL - pharmacology
Male
Nanoparticles
Protein Binding
Research Paper
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Summary:Chronic lymphocytic leukemia (CLL) remains incurable despite the introduction of new drugs. Therapies targeting receptors and pathways active specifically in malignant B cells might provide better treatment options. For instance, in B cell lymphoma, our group has previously shown that scavenger receptor type B-1 (SR-B1), the high-affinity receptor for cholesterol-rich high-density lipoproteins (HDL), is a therapeutic target. As evidence suggests that targeting cholesterol metabolism in CLL cells may have therapeutic benefit, we examined SR-B1 expression in primary CLL cells from patients. Unlike normal B cells that do not express SR-B1, CLL cells express the receptor. As a result, we evaluated cholesterol-poor synthetic HDL nanoparticles (HDL NP), known for targeting SR-B1, as a therapy for CLL. HDL NPs potently and selectively induce apoptotic cell death in primary CLL cells. HDL NPs had no effect on normal peripheral blood mononuclear cells from healthy individuals or patients with CLL. These data implicate SR-B1 as a target in CLL and HDL NPs as targeted monotherapy for CLL.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.14494