Afuco™ Anti-Human CTGF ADCC Recombinant Antibody (FG-3019), ADCC Enhanced

(A) The region of the FG-3019 binding epitope (CTGF amino acids 142 to 157, indicated in yellow) is superimposed on the structure of the collagen IIa VWC domain. By sequence homology, the general structural features of this domain are predicted to be conserved in CTGF and other CCN (connective tissue growth factor) proteins. The predicted FG-3019 binding site lies outside of a fibronectin-1-like module within the VWC domain of CTGF. A physical interaction between the VWC domain of Xenopus CTGF and TGF-β family members TGF-β1 and bone morphogenetic protein (BMP)-4 was reported. The location of the VWC domain relative to the insulin-like growth factor binding protein (IGF-BP), thrombospondin-1 (TSP1) and C-terminal cysteine knot (CT) homology domains of CCN family members is also indicated. (B) Recombinant human CTGF, CYR61 and NOV proteins (visualized by Coomassie blue in the upper panel) were analyzed by western blot using FG-3019, anti-CYR61 and anti-NOV antibodies. FG-3019 specifically bound CTGF without crossreacting with CYR61 or NOV.

Wang, Q.,Usinger,W.,Nichols,B.,Gray,J.,Xu,L.,Seeley,T.W., & Lin, A. (2011).Cooperative interaction of CTGF and TGF-β in animal models of fibrotic disease. Fibrogenesis & tissue repair, 4(1), 4.

(A, B) Liver and (C, D) kidney of 21-day-old animals coadministered TGF-β2 and CTGF; animals were treated with either (A, C) vehicle or (B, D) FG-3019. All agents were administered daily for 20 days beginning one day after birth. Arrows indicate regions of robust capsular fibrosis inhibited by FG-3019 treatment. Representative images are shown (all haematoxylin and eosin, original magnification × 200).

Wang, Q.,Usinger,W.,Nichols,B.,Gray,J.,Xu,L.,Seeley,T.W., & Lin, A. (2011).Cooperative interaction of CTGF and TGF-β in animal models of fibrotic disease. Fibrogenesis & tissue repair, 4(1), 4.

Hydroxyproline:proline (Hyp:Pro) ratios in renal tissues from UUO mice are expressed as the mean change above the mean Hyp:Pro ratio of unligated control kidneys (0.0446 ± 0.0005, n = 35). Mean renal Hyp:Pro ratio increases for the 10 and 30 mg/kg FG-3019 treatment groups (gray bars) were 20% and 15% lower than for the UUO kidneys of vehicle-treated controls (white bar), respectively. *P < 0.05 compared with UUO + vehicle (analysis of variance, Fisher's least significant difference).

Wang, Q.,Usinger,W.,Nichols,B.,Gray,J.,Xu,L.,Seeley,T.W., & Lin, A. (2011).Cooperative interaction of CTGF and TGF-β in animal models of fibrotic disease. Fibrogenesis & tissue repair, 4(1), 4.

Pulmonary hydroxyproline (Hyp) content (μg/lung) of bleomycin-treated mice is expressed as the mean change from Hyp content of healthy control lungs (285 ± 8 μg/lung, mean ± SEM, n = 10). Mean Hyp content (μg/lung) increases for the 3, 10 and 30 mg/kg FG-3019 treatment groups (gray bars) were 27, 38 and 13% lower than for the bleomycin mice treated with vehicle (white bar), respectively. *P = 0.056 vs. bleomycin + vehicle (ANOVA, Fisher's LSD).

Wang, Q.,Usinger,W.,Nichols,B.,Gray,J.,Xu,L.,Seeley,T.W., & Lin, A. (2011).Cooperative interaction of CTGF and TGF-β in animal models of fibrotic disease. Fibrogenesis & tissue repair, 4(1), 4.

One day old neonatal mice were injected SC daily for 7 days with 800 ng TGFβ2 alone or with 400 ng CTGF. FG-3019 was also administered to one group that received CTGF. The injections were then stopped for 4 days and the mice were sacrificed to examine the deposition of ECM components and cellular invasion. Panel A: the experimental design. Panel B: A cross section of the skin, SC space and underlying muscle from representative mice is shown. The arrows point out fibrotic response to the various treatments.

Finger,E.C.,Cheng, C.F.,Williams,T.R.,Rankin,E.B.,Bedogni,B.,Tachiki,L.,& Powell,M.B.(2014).CTGF is a therapeutic target for metastatic melanoma.Oncogene,33(9),1093.