In vivo targeting of B-cell lymphoma with glycan ligands of CD22.
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| Abstract |
Antibody-mediated cell depletion therapy has proven to provide significant clinical benefit in treatment of lymphomas and leukemias, driving the development of improved therapies with novel mechanisms of cell killing. A current clinical target for B-cell lymphoma is CD22, a B-cell-specific member of the sialic acid binding Ig-like lectin (siglec) family that recognizes alpha2-6-linked sialylated glycans as ligands. Here, we describe a novel approach for targeting B lymphoma cells with doxorubicin-loaded liposomal nanoparticles displaying high-affinity glycan ligands of CD22. The targeted liposomes are actively bound and endocytosed by CD22 on B cells, and significantly extend life in a xenograft model of human B-cell lymphoma. Moreover, they bind and kill malignant B cells from peripheral blood samples obtained from patients with hairy cell leukemia, marginal zone lymphoma, and chronic lymphocytic leukemia. The results demonstrate the potential for using a carbohydrate recognition-based approach for efficiently targeting B cells in vivo that can offer improved treatment options for patients with B-cell malignancies.
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| Authors | Weihsu C Chen, Gladys C Completo, Darren S Sigal, Paul R Crocker, Alan Saven, James C Paulson |
| Journal | Blood (Blood) Vol. 115 Issue 23 Pg. 4778-86 (Jun 10 2010) ISSN: 1528-0020 [Electronic] United States |
| PMID | 20181615 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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