Targeting of CD22-positive B-cell lymphoma cells by synthetic divalent sialic acid analogues

Schweizer A, Wöhner M, Prescher H, Brossmer R, Nitschke L (2012)


Publication Status: Published

Publication Type: Journal article

Publication year: 2012

Journal

Publisher: WILEY-BLACKWELL

Book Volume: 42

Pages Range: 2792-2802

Journal Issue: 10

DOI: 10.1002/eji.201242574

Abstract

CD22 is an inhibitory co-receptor of the B-cell receptor (BCR) on B cells. Since CD22 is ubiquitously expressed in the B-cell lineage and CD22 endocytosis can be triggered efficiently, antibodies and antibody-based immunotoxins against CD22 are used to target B cells both in B-cell lymphomas and leukemias, as well as in autoimmune diseases. CD22 recognizes a2,6-linked sialic acids as endogenous ligands. We have developed new synthetic sialosides as ligands for human CD22. These sialosides bind CD22 on human B cells with high affinity and can efficiently enhance IgM-triggered Ca2+ signaling. We coupled these sialosides to Pseudomonas exotoxin A to generate a novel CD22 ligand-based immunotoxin. This sialoside-exotoxin-A construct can specifically kill CD22-positive B-cell lymphoma cells. It binds specifically to CD22-positive B-cell lymphoma cells and is dominant over endogenous cis-ligands on the B-cell surface. The sialoside-exotoxin-A construct is efficiently internalized by endocytosis into B-cell lymphoma cell lines. Thus we show the development of a new therapeutic compound for targeting CD22 on human B cells, both for B-cell lymphoma, as well as for B-cell-mediated autoimmune diseases.

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APA:

Schweizer, A., Wöhner, M., Prescher, H., Brossmer, R., & Nitschke, L. (2012). Targeting of CD22-positive B-cell lymphoma cells by synthetic divalent sialic acid analogues. European Journal of Immunology, 42(10), 2792-2802. https://doi.org/10.1002/eji.201242574

MLA:

Schweizer, Astrid, et al. "Targeting of CD22-positive B-cell lymphoma cells by synthetic divalent sialic acid analogues." European Journal of Immunology 42.10 (2012): 2792-2802.

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