Oncotarget

Research Papers:

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

Kaylin M. McMahon, Cristina Scielzo, Nicholas L. Angeloni, Elad Deiss-Yehiely, Lydia Scarfo, Pamela Ranghetti, Shuo Ma, Jason Kaplan, Federica Barbaglio, Leo I. Gordon, Francis J. Giles, C. Shad Thaxton and Paolo Ghia _

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Oncotarget. 2017; 8:11219-11227. https://doi.org/10.18632/oncotarget.14494

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Abstract

Kaylin M. McMahon1,*, Cristina Scielzo2,3,*, Nicholas L. Angeloni1, Elad Deiss-Yehiely1, Lydia Scarfo2,3, Pamela Ranghetti2,3, Shuo Ma4, Jason Kaplan4,5, Federica Barbaglio3, Leo I. Gordon4, Francis J. Giles4,5, C. Shad Thaxton1,4,6,7, Paolo Ghia2,3

1Department of Urology, Feinberg School of Medicine, Northwestern University, Tarry, Chicago, IL, USA

2Università Vita-Salute San Raffaele, Milan, Italy

3Strategic Research Program On CLL and Unit of B cell Neoplasia, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy

4Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA

5Developmental Therapeutics Program of The Division of Hematology Oncology, Feinberg School of Medicine, Chicago, IL, USA

6Simpson Querrey Institute (SQI) for BioNanotechnology, Chicago, IL, USA

7International Institute for Nanotechnology, Evanston, IL, USA

*These authors equally contributed to this work

Correspondence to:

C. Shad Thaxton, email: [email protected]

Paolo Ghia, email: [email protected]

Keywords: lipoprotein, leukemia, scavenger receptor type B-I, nanoparticle, biomaterials

Received: June 29, 2016     Accepted: December 26, 2016     Published: January 04, 2017

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.


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