Targeting B lymphoma with nanoparticles bearing glycan ligands of CD22

被引:36
作者
Chen, Weihsu C. [2 ,3 ]
Sigal, Darren S. [1 ]
Saven, Alan [1 ]
Paulson, James C. [2 ,3 ]
机构
[1] Scripps Clin, Med Grp, Div Hematol & Oncol, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
[3] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
基金
美国国家卫生研究院;
关键词
CD22; B cell lymphoma; nanoparticles; LEUKEMIA; ROLES;
D O I
10.3109/10428194.2011.604755
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:208 / 210
页数:3
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