Targeting of CD22-positive B-cell lymphoma cells by synthetic divalent sialic acid analogues
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 leu...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2012
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| In: |
European journal of immunology
Year: 2012, Volume: 42, Issue: 10, Pages: 2792-2802 |
| ISSN: | 1521-4141 |
| DOI: | 10.1002/eji.201242574 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1002/eji.201242574 Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.201242574 
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| Author Notes: | Astrid Schweizer, Miriam Wöhner, Horst Prescher, Reinhard Brossmer and Lars Nitschke |
| Summary: | 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 α2,6-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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| Item Description: | First published: 10 July 2012 Gesehen am 08.06.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1521-4141 |
| DOI: | 10.1002/eji.201242574 |