Targeting of CD22-positive B-cell lymphoma cells by synthetic divalent sialic acid analogues.
Eur J Immunol
; 42(10): 2792-802, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22777817
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 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 Ca(2+) 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas
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Doenças Autoimunes
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Toxinas Bacterianas
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Linfócitos B
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Imunotoxinas
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Linfoma de Células B
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ADP Ribose Transferases
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Ácido N-Acetilneuramínico
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Fatores de Virulência
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Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico
Limite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Alemanha