In vivo targeting of B-cell lymphoma with glycan ligands of CD22.
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.
Chen
Weihsu C
WC
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
Completo
Gladys C
GC
Sigal
Darren S
DS
Crocker
Paul R
PR
Saven
Alan
A
Paulson
James C
JC
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008024:Ligands; D008081:Liposomes; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011134:Polysaccharides / Q000819:agonists* / Q000276:immunology; D051918:Sialic Acid Binding Ig-like Lectin 2; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; C497867:CD22 protein, human; D008024:Ligands; D008081:Liposomes; D011134:Polysaccharides; D051918:Sialic Acid Binding Ig-like Lectin 2; D004317:Doxorubicin