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

• 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
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.14494

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.