Abstract |
Autoantigen-specific B cells are culprits in the pathogenesis of many autoimmune diseases either through the production of autoreactive antibodies or as very effective antigen-presenting cells. A general depletion of B cells by a CD20-specific monoclonal IgG1 antibody has recently been validated as an effective strategy for treating rheumatoid arthritis. However, general elimination of B cells can lead to immunosuppression and increased risk of infection. In search for a more specific approach, we have generated a fusion protein for the antigen-specific targeting of autoreactive B cells for re-directed lysis by resting human T lymphocytes. We describe the design, purification and characterization of MOGxanti-CD3, a single-chain bispecific antibody fusion protein recognizing B cell receptors specific for the human myelin oligodendrocyte glycoprotein (MOG) and to CD3 on human T cells. MOGxAnti-CD3 induced selective and very efficient redirected lysis of MOG-reactive B cells through freshly isolated, unstimulated human T cells. Fusions between autoantigens and an anti-CD3 single-chain antibody may be suitable to develop very specific therapeutic approaches for the selective depletion of autoreactive B cells in autoimmune diseases.
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Authors | Marcel Zocher, Patrick A Baeuerle |
Journal | Molecular immunology
(Mol Immunol)
Vol. 41
Issue 5
Pg. 511-8
(Jul 2004)
ISSN: 0161-5890 [Print] England |
PMID | 15183929
(Publication Type: Journal Article)
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Chemical References |
- Antibodies
- Antibodies, Bispecific
- Autoantigens
- CD3 Complex
- MOG protein, human
- Myelin Proteins
- Myelin-Associated Glycoprotein
- Myelin-Oligodendrocyte Glycoprotein
- Recombinant Fusion Proteins
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Topics |
- Antibodies
(chemistry, immunology)
- Antibodies, Bispecific
- Antibody Specificity
- Autoantigens
- Autoimmunity
- B-Lymphocytes
(immunology)
- CD3 Complex
(immunology)
- Drug Design
- Humans
- Lymphocyte Depletion
(methods)
- Myelin Proteins
- Myelin-Associated Glycoprotein
(immunology)
- Myelin-Oligodendrocyte Glycoprotein
- Recombinant Fusion Proteins
(immunology)
- T-Lymphocytes
(immunology)
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