• Induced Model LPS responses, LPS/D-GAL, hepatic failure
  • Performed on TNF, TNFR1
  • Readouts Cytokine levels, Lethality, ALT activity

TNF as a therapeutic target

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.

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

Model Duration Read outs
Spontaneous Arthritis
6-7 weeks
6-7 weeks
5 weeks
7-12 weeks
12 weeks
-Clinical Scoring
-Serum cytokine levels
Induced Arthritis
Collagen Antibody Induced Arthritis (CAIA)
2 weeks -Weight
-Clinical Scoring
-Serum cytokine levels
DSS-induced colitis
13 days -Weight
-Clinical Scoring
-Local cytokine levels
Acute Inflammation
1-6 hours
24 hours
Serum cytokine levels
Survival & ALT activity levels