Development of a mouse-feline chimeric antibody against feline tumor necrosis factor-alpha

DOKI, Tomoyoshi; TAKANO, Tomomi; HOHDATSU, Tsutomu

Thus, the induction of feline anti-mouse antibodies in cats treated with mouse and chimeric mAb was investigated. As the feline anti-mouse antibody was increased in serum, the fTNF-alpha neutralization effect of mAb 2-4 was reduced in cats treated with mouse mAb 2-4 and 5 mg/kg chimeric mAb 2-4. That is, no neutralizing antibody against chimeric mAb 2-4 induction was observed in cats treated with 1 mg/ kg chimeric mAb 2-4, suggesting that feline anti-mouse antibody induction was prevented by modifying mouse mAb 2-4 to chimeric mAb 2-4. Accordingly, repeated administration of chimeric mAb 2-4 may not decrease the therapeutic effect in cats. However, in cats receiving 5 mg/kg chimeric mAb 2-4 administration, the neutralizing antibody against chimeric mAb 2-4 was induced after the 2nd administration, strongly suggesting that chimeric mAb 2-4 also induces production of neutralizing antibody against chimeric mAb 2-4 when administered at a high dose. A decrease in the therapeutic effect of infliximab due to production of neutralizing antibody against chimeric mAb has similarly been reported [7] . However, neutralizing antibody against chimeric mAb production can be inhibited by concomitant administration of an anti-inflammatory drug, methotrexate (MTX). MTX suppresses the humoral immune response and is thought to reduce production of antibody against chimeric mAb after infliximab administration [10, 11] . Concomitant MTX administration with chimeric mAb 2-4 may also inhibit production of neutralizing antibody against chimeric mAb. Future studies are necessary to investigate the applicability of concomitant MTX administration with chimeric mAb 2-4 in cats with FIP.