title: Synthetic high-density lipoproteins as targeted monotherapy for chronic lymphocytic leukemia.
abstract: 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.
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Tarry, Chicago, IL, USA.
authors.forename: Kaylin M
authors.initials: KM
authors.lastname: McMahon
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy.|Strategic Research Program On CLL and Unit of B cell Neoplasia, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Scielzo
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Tarry, Chicago, IL, USA.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Angeloni
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Tarry, Chicago, IL, USA.
authors.forename: Elad
authors.initials: E
authors.lastname: Deiss-Yehiely
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy.|Strategic Research Program On CLL and Unit of B cell Neoplasia, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Lydia
authors.initials: L
authors.lastname: Scarfo
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy.|Strategic Research Program On CLL and Unit of B cell Neoplasia, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ranghetti
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Ma
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.|Developmental Therapeutics Program of The Division of Hematology Oncology, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Kaplan
authors.affiliation: Strategic Research Program On CLL and Unit of B cell Neoplasia, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Barbaglio
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.|Developmental Therapeutics Program of The Division of Hematology Oncology, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Tarry, Chicago, IL, USA.|Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.|Simpson Querrey Institute (SQI) for BioNanotechnology, Chicago, IL, USA.|International Institute for Nanotechnology, Evanston, IL, USA.
authors.forename: C Shad
authors.initials: CS
authors.lastname: Thaxton
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy.|Strategic Research Program On CLL and Unit of B cell Neoplasia, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001667:Binding, Competitive; D015153:Blotting, Western; D018955:CD36 Antigens / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D053758:Nanoparticles; D011485:Protein Binding
chemical_list: D018955:CD36 Antigens; D008075:Lipoproteins, HDL
keywords: biomaterials; leukemia; lipoprotein; nanoparticle; scavenger receptor type B-I