RESEARCH - Anti-inflammatory and cartilage-protecting effects of an intra-articularly injected anti-TNF scFv (ESBA105)

[Guest guest]

Ann Rheum Dis. Published Online First: 16 March 2009.

doi:10.1136/ard.2008.105775

Extended Report

Anti-inflammatory and cartilage-protecting effects of an

intra-articularly injected anti-TNF scFv (ESBA105) designed for local

therapeutic use

D M Urech 1, U e 1, S Ewert 1, V Schlosser 1, M Ottiger 1, K

Polzer 2, G Schett 2 and P Lichtlen 1*

1 ESBATech AG, Switzerland

2 Institute for Clinical Immunology, University of Erlangen-Nuremberg, Germany

Abstract

Objectives: To demonstrate that a single-chain antibody (scFv) against

TNF- (ESBA105) has efficacy comparable to a full length anti-TNF- IgG

(infliximab). Furthermore, to evaluate whether ESBA105 has all

properties required for local treatment of arthritis and to

investigate its discriminative tissue penetration properties.

Methods: In vivo efficacy was measured in arthritis of the knee joint

induced by intra-articular (i.a.) injection of recombinant human TNF-

(rhTNF-) 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 i.a. and

i.v. administration.

Results: In cell culture, ESBA105 showed highly similar TNF-

inhibitory potency as infliximab. In vivo, ESBA105 inhibited rhTNF-

induced synovial inflammation in rats with efficacy again comparable

to infliximab. An 11-fold molar excess of ESBA105 over rhTNF- resulted

in 90% inhibition of knee joint swelling, inflammatory infiltrates as

well as proteoglycan loss from cartilage. In ex vivo studies of bovine

cartilage, ESBA105 penetrated well into cartilage whereas infliximab

remained on the surface of the cartilage. In vivo, following

[125I]-ESBA105 i.a. injection into the knee joint of rabbits, rapid

penetration into synovial tissue, cartilage and surrounding tissues

was observed.

Conclusions: ESBA105 potently inhibits inflammation and prevents

cartilage damage triggered by TNF-. In contrast to a full length IgG,

ESBA105 also penetrates into cartilage and can be expected to reverse

the TNF- induced catabolic state of articular cartilage in

arthritides.

http://ard.bmj.com/cgi/content/abstract/ard.2008.105775v1

Not an MD