In vivo targeting of hematopoetic cells with glycan ligands of siglecs

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DESCRIPTION (provided by applicant): CD22 is a B lymphocyte specific glycan binding protein that participates in regulation of B cell receptor signaling. The extra-cellular domain recognizes sialic acid containing glycans as ligands that regulate its activity during B cell activation and differentiation. Because it is specifically expressed on B cells, CD22 is also a clinical target for antibody based cell depletion therapies for treatment of B cell lymphoma and inflammatory autoimmune disease. We have developed an approach for targeting B cells using multivalent glycan ligands of CD22. In this project we will develop B cell targeted liposomes using glycan ligands of CD22, and test their utility for depletion of B cells in murine models of disease. The major objectives of the project are: 1) Develop chemotherapeutic loaded liposomes displaying ligands of human CD22 that efficiently and specifically target and kill B cells. 2) Assess the in vivo efficacy of CD22 targeted liposome formulations in a murine model of human B cell lymphoma. 3) Test the ability of CD22 targeted liposomes to bind to cancer cells in the blood of human B cell leukemia and non-Hodgkin's B cell lymphoma patients. 4) Determine if B cell depletion with CD22 targeted chemotherapeutic liposomes exhibit efficacy in a murine model of autoimmune disease. If successful, the results may lead to the development of cell-targeted therapies for treatment of B cell malignancies and inflammatory autoimmune diseases mediated by B cells.