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Knockout TNF- α when treating FIP

Doki T, Takano T, Hohdatsu T.  Development of a mouse-feline chimeric antibody against feline tumor necrosis factor-alpha.  J Vet Med Sci. 2016 Jun 4. 
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Feline infectious peritonitis (FIP) continues to be a fatal disease of cats, in particular, in young cats under 2 years old.  It is caused by virulent feline coronavirus for which an infected cat’s cellular immunity is not strong enough to control the infection.  Functional cellular immunity is important in controlling virus infection and it is mediated by T lymphocytes.  During FIP progression, low lymphocyte count occurs, which further impairs the cat’s ability to fight the infection and a severely low count is considered a poor prognostic indicator for the disease.  Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine secreted mainly by macrophages infected by virus and other immune cells, is thought to cause the severe decrease in the lymphocyte count.

Researchers from School of Veterinary Medicine, Kitasato University in Towada, Japan previously reported prevention of disease progression to FIP by inhibition of TNF- alpha after administering a neutralizing mouse anti-fTNF-α, monoclonal antibody.  When anti-fTNF-α, mouse mAb was administered to cats with FIP, their survival time and quality of life were improved (Doki T, Takano T, Kawagoe K, et al., 2016).  However, administration of mouse mAb to cats increased risk of adverse reactions (e.g., anaphylaxis, develop of anti-mouse antibodies).

In this study, they prepared and administered a mouse-feline chimeric mAb (chimeric mAb 2-4) by modifying the mouse anti-fTNF-α, mAb 2-4 and investigated it’s ability to cause adverse reactions and to neutralize fTNF-α, activity. In conclusion, the chimeric mAb 2-4 administered to cats still induced a feline anti-mouse antibody response, but it was decreased compared to that after mouse mAb 2-4 administration. These results warrant further investigation on the dose and dosing frequency of chimeric mAb 2-4 appropriate for effective treatment of cats with FIP.   It can be envisioned that a TNF-α inhibitor will be part of a treatment cocktail for treating FIP. (GO)

See also:

Doki T, Takano T, Kawagoe K, et al. Therapeutic effect of anti-feline TNF-alpha monoclonal antibody for feline infectious peritonitis. Res Vet Sci. 2016 Feb;104:17-23.