Recombinant chimeric OKT3/IgM antibodies for immune suppression: evaluation in a human CD3 transgenic mouse model
| Autor: | Ingrid Choi, Alexandra Bähre, Björn Cochlovius, Melvyn Little, Wolfgang E. Schmitt |
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| Rok vydání: | 2001 |
| Předmět: |
Time Factors
CD3 Complex medicine.drug_class CD3 medicine.medical_treatment T cell Recombinant Fusion Proteins Immunology Mice Transgenic Monoclonal antibody law.invention Interferon-gamma Mice Immune system law medicine Immunology and Allergy Animals Humans Inflammation biology Tumor Necrosis Factor-alpha Molecular biology Cytokine medicine.anatomical_structure Immunoglobulin M Monoclonal Models Animal biology.protein Recombinant DNA Interleukin-2 Antibody Immunosuppressive Agents Muromonab-CD3 |
| Zdroj: | Immunology letters. 80(2) |
| ISSN: | 0165-2478 |
| Popis: | ScOKT3-gammaDeltaIgM VAEVD is a recombinant chimeric anti-CD3 antibody variant consisting of the light and heavy variable binding domains of the OKT3 monoclonal antibody and the CH3 and CH4 domains of a human IgM mutation linked by a human IgG3 hinge region. Due to the IgM Fc domains, scOKT3-gammaDeltaIgM VAEVD antibodies are able to form polymeric structures. Independent of their polymerization state, they possess in vitro CD3 modulating and immunosuppressive properties while inducing only minimal T cell activation compared to their monoclonal counterpart. To evaluate the in vivo efficacy of the antibodies, an adjuvant-induced chronic inflammation was established in human CD3 transgenic mice. Administration of four doses of 15 microg of isolated scOKT3-gammaDeltaIgM VAEVD monomers and pentamers significantly reduced diameters of inflamed ankle joints in a manner comparable to the monoclonal antibody OKT3. Additionally, the antibody treatment lead to a significant reduction of the cytokine levels (IL-2, TNF-alpha and INF-gamma) in the mice's sera. These results suggest that scOKT3-gammaDeltaIgM VAEVD antibodies may provide a useful alternative to the OKT3 mAb for clinical immunosuppressive treatment for auto-aggressive diseases or for organ-transplantation. |
| Databáze: | OpenAIRE |
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