Targeting B lymphoma with nanoparticles bearing glycan ligands of CD22

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.

Keywords::

• CD22
• B cell lymphoma
• nanoparticles

Acknowledgement

This paper is part of the proceedings and papers from the International Hairy Cell Leukemia Consortium Meeting “Treatment of Hairy Cell Leukemia in its Second Half Century”, held at the NIH, Bethesda, Maryland, USA April 26-27, 2010, which was featured in this journal, Volume 52, Number S2 (June 2011). This work was supported by National Institutes of Health grants R01-AI050143 and R01-GM060938.

Potential conflict of interest:

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