TNF

TNF (Tumor Necrosis Factor) is a pleiotropic cytokine with leading role in disease pathogenesis and therefore is a very attractive target for the treatment of a diverse array of diseases, including autoimmunity, cancer, infectious diseases, and graft-versus-host disease.
pleiotropic cytokine

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TNF as a therapeutic target

TNF inhibitors/blockers, include biologics and small molecule inhibitors that target diseases like rheumatoid arthritis (RA), juvenile arthritis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, ulcerative colitis (UC), and Crohn’s disease. Several blockers, innovator compounds as well as biosimilars, are currently available in the market including Adalimumab (Humira), Adalimumab-atto (Amjevita), a biosimilar to Humira, Certolizumab pegol (Cimzia), Etanercept (Enbrel), Etanercept-szzs (Ereizi), a biosimilar to Enbrel, Golimumab (Simponi, Simponi Aria), Infliximab (Remicade), Infliximab-dyyb (Inflectra), a biosimilar to Remicade. A continuing interest in the field of TNF blockade is reflected in current efforts to develop next generation anti-TNF therapeutics.

The humanized TNF mouse models

An array of mouse models humanized for TNF, in combination with an array of spontaneous or induced disease models, offer ideal preclinical platforms for the efficient evaluation of therapeutics targeting the inhibition of human TNF.

Preclinical Platforms for the evaluation of TNF targeting therapeutics

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Tg197

A humanized mouse model that overexpresses human TNF and develops spontaneously chronic arthritis pathology.

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Tg197hTNFR1Kl

A humanized TNF-TNFR1 arthritis model suitable for testing and comparing the therapeutic effects of anti-hTNFR1 and anti-hTNF biologics.

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Tg5453

A unique tool for the assessment of the efficacy of anti-hTNF agents in the blockade of the transmembrane form of human TNF.

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Tg3647

A humanized mouse model that overexpresses human TNF and develops late onset, slow progression, arthritis pathology.

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TNFΔARE/+ hTNFR1KI

A mouse mutant with deregulated TNF expression resulting in the spontaneous development of arthritis together with Crohn’s –like intestinal inflammation.

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CAIA

An short duration induced arthritis model that, in combination to hTNF transgenic mice, allows the fast and efficient evaluation of therapeutics targeting TNF .

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Tg197/ DSS Colitis

DSS colitis in Tg197 mice offers an acute disease model suitable for testing the efficacy of anti-hTNF biologics in intestinal inflammation.

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LPS

LPS induced responses in hTNF transgenic micelle the basis of a unique fast screening platform for the evaluation of anti-hTNF therapeutics.

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LPS/GaIN

LPS/GalN epatic failure induced in hTNF transgenic mice offers a highly sensitive screening platform for the efficacy evaluation of anti-hTNF therapeutics.