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 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.
['McMahon|Kaylin M|KM|', 'Scielzo|Cristina|C|', 'Angeloni|Nicholas L|NL|', 'Deiss-Yehiely|Elad|E|', 'Scarfo|Lydia|L|', 'Ranghetti|Pamela|P|', 'Ma|Shuo|S|', 'Kaplan|Jason|J|', 'Barbaglio|Federica|F|', 'Gordon|Leo I|LI|', 'Giles|Francis J|FJ|', 'Thaxton|C Shad|CS|', 'Ghia|Paolo|P|']
D017209:Apoptosis D001667:Binding, Competitive D015153:Blotting, Western D018955:CD36 Antigens D002478:Cells, Cultured D005260:Female D005434:Flow Cytometry D006801:Humans D015451:Leukemia, Lymphocytic, Chronic, B-Cell D007963:Leukocytes, Mononuclear D008075:Lipoproteins, HDL D008297:Male D053758:Nanoparticles D011485:Protein Binding
lipoprotein leukemia nanoparticle biomaterials scavenger receptor type B-I