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

Weihsu C. Chen, Gladys C. Completo, Darren S. Sigal, Paul R. Crocker, Alan Saven, James C. Paulson (Lead / Corresponding author)

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    126 Citations (Scopus)

    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 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)

    Original languageEnglish
    Pages (from-to)4778-4786
    Number of pages9
    JournalBlood
    Volume115
    Issue number23
    Early online date24 Feb 2010
    DOIs
    Publication statusPublished - 10 Jun 2010

    Keywords

    • Pegylated liposomal doxorubicin
    • Non-Hodgkins lymphoma
    • Drug delivery
    • Inotuzumzb ozogamicin
    • Cytotoxic activity
    • Flow cytometry
    • CIS ligands
    • Sialoadhesin
    • Chemotherapy
    • Efficacy

    Cite this

    Chen, W. C., Completo, G. C., Sigal, D. S., Crocker, P. R., Saven, A., & Paulson, J. C. (2010). In vivo targeting of B-cell lymphoma with glycan ligands of CD22. Blood, 115(23), 4778-4786. https://doi.org/10.1182/blood-2009-12-257386