Liposomes modified by carbohydrate ligands can target B cells for the treatment of B-cell lymphomas

Abstract

Evaluation of: Chen WC, Completo GC, Sigal DS, Crocker PR, Saven A, Paulson JC. In vivo targeting of B-cell lymphoma with glycan ligands of CD22. Blood 115(23), 4778-4786 (2010). A strategy has been developed to deliver selectively chemotherapeutic drugs to B cells by employing doxorubicin-loaded liposomes modified by a ligand for the B-cell-specific cell-surface protein CD22, also known as Siglec-2. The liposomes bound in a rapid and saturable manner to the human Burkitt lymphoma Daudi B-cell line and exhibited significantly higher cytotoxicity in vitro and in vivo compared with similar untargeted liposomes. The CD22-targeted liposome bound to B cells isolated from lymphoma patients and although binding was proportional to CD22 expression on the cell surface, low levels of expression on chronic lymphocytic leukemia cells were sufficient to effect cell neutralization. The glycan-based strategy for delivery of chemotherapeutic agents may provide a new strategy for the treatment of B-cell lymphomas.

Figure 1. The chemical structure of the ^BPCNeuAc modified with a lipid for incorporation into doxorubicin-modified micelles

The terminal monosaccharide is a modified sialic acid moiety. The biphenyl of the sialic acid moiety (highlighted in blue) significantly enhances the affinity for binding to CD22.