tailieunhanh - Antibody-mediated delivery of IL-10 inhibits the progression of established collagen-induced arthritis

of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang-Paulistrasse 10, CH-8093 Zurich, Switzerland 2Institute of Pathology, Helios Klinikum Erfurt, Nordhaeuser Strasse 74, D-99089 Erfurt, Germany Corresponding author: Dario Neri, neri@ Received: 12 Oct 2006 Revisions requested: 6 Dec 2006 Revisions received: 12 Jan 2007 Accepted: 29 Jan 2007 Published: 29 Jan 2007 Arthritis Research & Therapy 2007, 9:R9 (doi:) This article is online at: © 2007 Trachsel et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the. | Available online http content 9 1 R9 Research article Antibody-mediated delivery of IL-10 inhibits the progression of established collagen-induced arthritis Eveline Trachsel1 Frank Bootz1 Michela Silacci1 Manuela Kaspar1 Hartwig Kosmehl2 and Dario Neri1 institute of Pharmaceutical Sciences Department of Chemistry and Applied Biosciences ETH Zurich Wolfgang-Paulistrasse 10 CH-8093 Zurich Switzerland institute of Pathology Helios Klinikum Erfurt Nordhaeuser Strasse 74 D-99089 Erfurt Germany Corresponding author Dario Neri neri@ Received 12 Oct 2006 Revisions requested 6 Dec 2006 Revisions received 12 Jan 2007 Accepted 29 Jan 2007 Published 29 Jan 2007 Arthritis Research Therapy 2007 9 R9 doi ar2115 This article is online at http content 9 1 R9 2007 Trachsel et al. licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Open Access Abstract The antibody-mediated targeted delivery of cytokines to sites of disease is a promising avenue for cancer therapy but it is largely unexplored for the treatment of chronic inflammatory conditions. Using both radioactive and fluorescent techniques the human monoclonal antibodies L19 and G11 specific to two markers of angiogenesis that are virtually undetectable in normal adult tissues were found to selectively localize at arthritic sites in the murine collagen-induced model of rheumatoid arthritis following intravenous . administration. The same animal model was used to study the therapeutic action of the L19 antibody fused to the cytokines IL-2 tumour necrosis factor TNF and IL-10. Whereas L19-IL-2 and L19-TNF treatment led to increased arthritic scores and paw swellings the fusion protein L19-IL-10 displayed a therapeutic .