Anti-inflammatory and cartilage-protecting effects of an intra-articularly injected anti-TNFα single-chain Fv antibody (ESBA105) designed for local therapeutic use. Issue 2 (16th March 2009)

• Record Type: Journal Article
• Authors: Urech, D M; Feige, U; Ewert, S; Schlosser, V; Ottiger, M; Polzer, K; Schett, G; Lichtlen, P
• Is Part Of: Annals of the rheumatic diseases. Volume 69:Issue 2(2010)
• Page Start: 443
• Page End: 449
• Publication Date: 2009-03-16
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2008.105775
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objectives: (1) To show that a single-chain Fv antibody (scFv) against tumour necrosis factor α (TNFα) (ESBA105) has efficacy comparable to a full length anti-TNFα IgG (infliximab); (2) to evaluate whether ESBA105 has all the properties required for the local treatment of arthritis; and (3) to investigate its discriminative tissue penetration properties. Methods: In vivo efficacy was measured in arthritis of the knee joint induced by the intra-articular injection of recombinant human TNFα (rhTNFα) in Lewis rats. Cartilage penetration of scFv (ESBA105) and full length IgG (infliximab) were studied in bovine cartilage specimens ex vivo. Tissue penetration, biodistribution and pharmacokinetics of ESBA105 were followed and compared after intra-articular and intravenous administration. Results: In cell culture, ESBA105 showed similar TNFα inhibitory potency to infliximab. In vivo, ESBA105 inhibited rhTNFα-induced synovial inflammation in rats with efficacy again comparable to infliximab. An 11-fold molar excess of ESBA105 over rhTNFα resulted in 90% inhibition of knee joint swelling, inflammatory infiltrates and proteoglycan loss from cartilage. In ex vivo studies of bovine cartilage, ESBA105 penetrated well into the cartilage whereas infliximab remained on the surface. In vivo, rapid penetration into the synovial tissue, cartilage and surrounding tissues was observed following intra-articular injection of [ 125 I]-ESBA105 into the knee joint of rabbits. Conclusions: ESBA105 potently inhibits inflammation and prevents cartilage damage triggered by TNFα. In contrast to a full length IgG, ESBA105 also penetrates into cartilage and can be expected to reverse the TNFα-induced catabolic state of articular cartilage in arthritides.