Simultaneous targeting of TNF and Ang2 with a novel bispecific antibody enhances efficacy in an in vivo model of arthritis
| Autor: | David M. Hilbert, Palanisamy Kanakaraj, Carlos F. Barbas, Peter Kiener, Xiao-Tao Yao, Rodger Smith, Rutul R. Shah, Bridget A. Puffer, David W. Lafleur, Geping Wang, Dimki R. Patel, Ernest Boyd, Shashi Kaithamana, Spandana Kankanala, Viktor Roschke, Rajesh Krishnamurthy |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_treatment
Recombinant Fusion Proteins Immunology TNF Arthritis Zybody Mice Transgenic Antibodies Monoclonal Humanized Cell Line Angiopoietin-2 Arthritis Rheumatoid Mice Immune system Psoriasis Report Antibodies Bispecific Adalimumab Immunology and Allergy Medicine Animals Humans Inflammation biology business.industry Tumor Necrosis Factor-alpha Immunosuppression medicine.disease Ang2 bispecific antibody Disease Models Animal Treatment Outcome arthritis Rheumatoid arthritis biology.protein Tumor necrosis factor alpha Antibody business medicine.drug |
| Zdroj: | mAbs |
| ISSN: | 1942-0870 1942-0862 |
| Popis: | Despite the clinical success of anti-tumor necrosis factor (TNF) therapies in the treatment of inflammatory conditions such as rheumatoid arthritis, Crohn disease and psoriasis, full control of the diseases only occurs in a subset of patients and there is a need for new therapeutics with improved efficacy against broader patient populations. One possible approach is to combine biological therapeutics, but both the cost of the therapeutics and the potential for additional toxicities needs to be considered. In addition to the various mediators of immune and inflammatory pathways, angiogenesis is reported to contribute substantially to the overall pathogenesis of inflammatory diseases. The combination of an anti-angiogenic agent with anti-TNF into one molecule could be more efficacious without the risk of severe immunosuppression. To evaluate this approach with our Zybody technology, we generated bispecific antibodies that contain an Ang2 targeting peptide genetically fused to the anti-TNF antibody adalimumab (Humira®). The bispecific molecules retain the binding and functional characteristics of the anti-TNF antibody, but with additional activity that neutralizes Ang2. In a TNF transgenic mouse model of arthritis, the bispecific anti-TNF-Ang2 molecules showed a dose-dependent reduction in both clinical symptoms and histological scores that were significantly better than that achieved by adalimumab alone. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|