An antibody to IP-10 is a potent antagonist of cell migration in vitro and in vivo and does not affect disease in several animal models of inflammation

作者：Byrne Fergus R^*; Winters Aaron; Brankow David; Hu Sylvia; Juan Todd; Steavenson Shirley; Doellgast George; Kuchimanchi Kamesh; Brown Heather; Anderson Sharon; Smelt Sara; Sullivan Tim; Alcorn Dina; Tocker Joel; Dean Charley Jr; Macmaster John; Kirchner Jacqueline; Buys Janet; Manoukian Raffi; Jiao Eric; Zou Xiaoming; Campanella Gabriele S; Siu Gerald

来源：Autoimmunity, 2009, 42(3): 171-182.

DOI：10.1080/08916930802629547

• Inflammation
• mouse
• chemokine
• IP-10
• monoclonal antibody

IP-10 secretion is induced by pro-inflammatory cytokines and mediates the migration of CXCR3 cells. Its elevation in clinical samples has been associated with multiple inflammatory diseases and its antagonism has been reported to be effective in several animal models of inflammatory disease. We generated a mouse anti-mouse IP-10 monoclonal antibody (mAb; Clone 20A9) that specifically bound murine IP-10 with high affinity and inhibited in vitro IP-10 induced BaF3/mCXCR3 cell migration with an IC50 of 4nM. The 20A9 mAb was completely absorbed in vivo and had dose proportional pharmacokinetic exposure with a serum half life of 2.4-6 days. The 20A9 mAb inhibited IP-10 mediated T-cell recruitment to the airways, indicating that it is effective in vivo. However, administration of the 20A9 mAb had no significant effect on disease in mouse models of delayed type hypersensitivity, collagen induced arthritis, cardiac allograft transplantation tolerance, EAE or CD4 CD45RBHi T-cell transfer-induced IBD. These data suggest that the 20A9 mAb can antagonize IP-10 mediated chemotaxis in vitro and in vivo and that this is insufficient to cause a therapeutic benefit in multiple mouse models of inflammatory disease.

• 出版日期2009