In vivo targeting of B-cell lymphoma with glycan ligands of CD22

被引:167
作者
Chen, Weihsu C. [1 ,2 ]
Completo, Gladys C. [1 ,2 ]
Sigal, Darren S. [3 ]
Crocker, Paul R. [4 ]
Saven, Alan [3 ]
Paulson, James C. [1 ,2 ]
机构
[1] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[3] Scripps Clin Med Grp, Div Hematol & Oncol, La Jolla, CA USA
[4] Univ Dundee, Coll Life Sci, Wellcome Trust Bioctr, Dundee, Scotland
基金
美国国家卫生研究院;
关键词
PEGYLATED LIPOSOMAL DOXORUBICIN; NON-HODGKINS-LYMPHOMA; DRUG-DELIVERY; INOTUZUMAB OZOGAMICIN; CYTOTOXIC ACTIVITY; FLOW-CYTOMETRY; CIS LIGANDS; SIALOADHESIN; CHEMOTHERAPY; EFFICACY;
D O I
10.1182/blood-2009-12-257386
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 alpha 2-6-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. (Blood. 2010;115(23):4778-4786)
引用
收藏
页码:4778 / 4786
页数:9
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