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Review
. 2012 Feb;53(2):208-10.
doi: 10.3109/10428194.2011.604755. Epub 2011 Aug 24.

_targeting B lymphoma with nanoparticles bearing glycan ligands of CD22

Weihsu C Chen  1 , Darren S Sigal, Alan Saven, James C Paulson
Affiliations
Review

_targeting B lymphoma with nanoparticles bearing glycan ligands of CD22

Weihsu C Chen et al. Leuk Lymphoma. 2012 Feb.

Abstract

CD22 is a member of the siglec (sialic acid-binding immunoglobulin-like lectin) family expressed on B cells that recognizes glycans of glycoproteins as ligands. Because siglecs exhibit restricted expression on one or a few leukocyte cell types, they have gained attention as attractive _targets for cell-directed therapies. Several antibody-based therapies _targeting CD22 (Siglec-2) are currently in clinical trials for the treatment of hairy cell leukemia and other B cell lymphomas. As an alternative to antibodies we have developed liposomal nanoparticles decorated with glycan ligands of CD22 that selectively _target B cells. Because CD22 is an endocytic receptor, ligand-decorated liposomes are bound by CD22 and rapidly internalized by the cell. When loaded with a toxic cargo such as doxorubicin, they are efficacious in prolonging life in a Daudi B cell lymphoma model. These B cell _targeted nanoparticles have been demonstrated to bind and kill malignant B cells from patients with hairy cell leukemia, marginal zone lymphoma and chronic lymphocytic leukemia. The results demonstrate the potential of using CD22 ligand-_targeted liposomal nanoparticles as an alternative approach for the treatment of B cell malignancies.

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Figures

Figure 1
Figure 1
Liposomal nanoparticles displaying glycan ligands of CD22 for _targeting and killing hairy cells leukemia. (A) Schematic illustration of a doxorubicin-loaded liposomal formulation comprising BPCNeuAc-pegylated lipids for active _targeting to CD22. (B) BPCNeuAc-liposomes bind to hairy cells in the patient peripheral blood. Data shown are FACS analysis of HCL (red) and normal B cells (green), using fluorescently labeled BPCNeuAc-liposomes or naked liposomes. (C) Cytotoxicity of BPCNeuAc-liposomes toward HCL. Patient blood cells were subjected to liposomal doxorubicin at 10 or 40 µM for 1 hr. Cells were thoroughly washed and incubated in fresh medium for an additional 5 days prior to viability assay. Data shown are percent viability (means of triplicate ± s.d.) of patient blood lymphocytes evaluated by the standard MTT assay. Cells left untreated were defined as the maximal cell viability. Complete cell killing was determined from the Triton X-100 lysed cells. *P < 0.05 as compared to control treatments of naked-liposomes. Representative data from one of four samples are shown.
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