| Autor: |
Ventura Elisa, Balza Enrica, Borsi Laura, Tutolo Giorgia, Carnemolla Barbara, Castellani Patrizia, Zardi Luciano |
| Jazyk: |
angličtina |
| Rok vydání: |
2011 |
| Předmět: |
|
| Zdroj: |
BMC Biotechnology, Vol 11, Iss 1, p 104 (2011) |
| Druh dokumentu: |
article |
| ISSN: |
1472-6750 |
| DOI: |
10.1186/1472-6750-11-104 |
| Popis: |
Abstract Background Ligand-targeted approaches have proven successful in improving the therapeutic index of a number of drugs. We hypothesized that the specific targeting of TNF-alpha antagonists to inflamed tissues could increase drug efficacy and reduce side effects. Results Using uteroglobin (UG), a potent anti-inflammatory protein, as a scaffold, we prepared a bispecific tetravalent molecule consisting of the extracellular ligand-binding portion of the human TNF-alpha receptor P75 (TNFRII) and the scFv L19. L19 binds to the ED-B containing fibronectin isoform (B-FN), which is expressed only during angiogenesis processes and during tissue remodeling. B-FN has also been demonstrated in the pannus in rheumatoid arthritis. L19-UG-TNFRII is a stable, soluble homodimeric protein that maintains the activities of both moieties: the immuno-reactivity of L19 and the capability of TNFRII to inhibit TNF-alpha. In vivo bio-distribution studies demonstrated that the molecule selectively accumulated on B-FN containing tissues, showing a very fast clearance from the blood but a very long residence time on B-FN containing tissues. Despite the very fast clearance from the blood, this fusion protein was able to significantly improve the severe symptomatology of arthritis in collagen antibody-induced arthritis (CAIA) mouse model. Conclusions The recombinant protein described here, able to selectively deliver the TNF-alpha antagonist TNFRII to inflamed tissues, could yield important contributions for the therapy of degenerative inflammatory diseases. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
