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Selective silencing of auto-aggressive B cells in animal models of autoimmune diseases

English title Selective silencing of auto-aggressive B cells in animal models of autoimmune diseases
Applicant Izui Shozo
Number 110719
Funding scheme SCOPES
Research institution Département de Pathologie et Immunologie Faculté de Médecine / CMU Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Immunology, Immunopathology
Start/End 01.10.2005 - 31.12.2007
Approved amount 54'000.00
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Keywords (5)

Autoimmunity; Systemic lupus erythematosus; Inhibitory receptors; Chimeric antibodies; Immunotherapy

Lay Summary (English)

Lead
Lay summary
The therapeutic approaches used at present to treat autoimmune diseases are not satisfactory as they are not targeted and induce either 1) general immunosuppression; 2) general suppression of inflammation or 3) a long-lasting elimination of all B cells regardless of their antigen specificity. We propose a novel strategy for the selective silencing of disease-associated autoreactive B cells.
The disease-associated DNA-specific B lymphocytes in SLE are logical targets for a selective therapeutic intervention. Our preliminary studies show that it is possible to inhibit selectively the production of IgG anti-DNA antibodies and to suppress disease activity in mice with spontaneous lupus by administering to them chimeric antibodies that cross-link their DNA-binding immunoglobulin receptors with inhibitory B cell receptors.
We shall produce a series of hybrid molecules by coupling monoclonal anti-mouse FcRIIB and anti-CD22 antibodies to DNA-mimotope peptides. Their immunomodulatory activity will be tested in young disease-free (6-7 weeks old) and sick (4-5 months old) lupus-prone MRL/lpr mice. Such chimeric antibodies may provide a platform for the development of highly selective therapeutic approaches in autoimmune diseases.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

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