title: Targeting B lymphoma with nanoparticles bearing glycan ligands of CD22.
abstract: 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.
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Weihsu C
authors.initials: WC
authors.lastname: Chen
authors.forename: Darren S
authors.initials: DS
authors.lastname: Sigal
authors.forename: Alan
authors.initials: A
authors.lastname: Saven
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D008024:Ligands; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology*; D053758:Nanoparticles; D011134:Polysaccharides / Q000276:immunology / Q000378:metabolism*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D011134:Polysaccharides; D051918:Sialic Acid Binding Ig-like Lectin 2