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.

• Authors: Weihsu C Chen, Darren S Sigal, Alan Saven, James C Paulson
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 53 Issue 2 Pg. 208-10 (Feb 2012) ISSN: 1029-2403 [Electronic] United States
• PMID: 21756025 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Antineoplastic Agents
• Ligands
• Polysaccharides
• Sialic Acid Binding Ig-like Lectin 2

Topics

• Antineoplastic Agents (therapeutic use)
• Humans
• Ligands
• Lymphoma, B-Cell (drug therapy, immunology)
• Nanoparticles
• Polysaccharides (immunology, metabolism)
• Sialic Acid Binding Ig-like Lectin 2 (chemistry, metabolism)