RESEARCH - Anti-inflammatory and cartilage protecting effects of an intra-articularly injected anti-TNF-alpha antibody

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Ann Rheum Dis 2010;69:443-449 doi:10.1136/ard.2008.105775

Basic and translational research

Extended report

Anti-inflammatory and cartilage-protecting effects of an

intra-articularly injected anti-TNFα single-chain Fv antibody

(ESBA105) designed for local therapeutic use

D M Urech1, U e1, S Ewert1, V Schlosser1, M Ottiger1, K Polzer2, G

Schett2, P Lichtlen1

+ Author Affiliations

1ESBATech AG, Schlieren, Switzerland

2Department of Internal Medicine 3 and Institute for Clinical

Immunology, University of Erlangen-Nuremberg, Erlangen, Germany

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 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 [125I]-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.

http://ard.bmj.com/content/69/2/443.abstract?etoc

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