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In vivo targeting of b-cell lymphoma with glycan ligands of cd22

Academic Article
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Overview

authors

  • Chen, W. C.
  • Completo, G. C.
  • Sigal, D. S.
  • Crocker, P. R.
  • Saven, A.
  • Paulson, James

publication date

  • June 2010

journal

  • Blood  Journal

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.

subject areas

  • Animals
  • Antibiotics, Antineoplastic
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Doxorubicin
  • Drug Delivery Systems
  • Humans
  • Ligands
  • Liposomes
  • Lymphoma, B-Cell
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Polysaccharides
  • Sialic Acid Binding Ig-like Lectin 2
  • Xenograft Model Antitumor Assays
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Identity

PubMed Central ID

  • PMC2890185

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2009-12-257386

PubMed ID

  • 20181615
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Additional Document Info

start page

  • 4778

end page

  • 4786

volume

  • 115

issue

  • 23

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