A novel llama antibody targeting Fn14 exhibits anti-metastatic activity in vivo

Abstract

(2014) A novel llama antibody targeting Fn14 exhibits anti-metastatic activity in vivo, mAbs, 6:1, 297-308,

Quantitative analysis of cell surface antigen-antibody interaction using Gaussia princeps luciferase antibody fusion proteins

“…As shown previously, 16 nonoligomerized 18D1-IgG1 largely failed to trigger interleukin (IL)8 production in WiDr cells up to concentrations of 10 mg/ml, while it triggered strong IL8 production already at concentrations below 1 mg/ml in the presence of protein G (Fig. 4A).…”

“…We therefore evaluated whether GpL-tagging is also applicable and useful for conventional antibodies. Initially, we generated different GpL fusion protein formats of the Fn14-specific human IgG1 antibody 18D1 (18D1-IgG) 16 to identify the position in the IgG1 molecule that is best suited for linkage of the GpL domain. In one antibody GpL fusion protein format, the GpL domain was linked to the C-terminus of the heavy chain of 18D1 (GpL (CT-HC) -18D1-IgG1), while in 2 other formats the GpL domain has been linked to the N-terminus (GpL (NT-LC) -18D1-IgG1) or C-terminus (GpL (CT-LC) -18D1-IgG1) of the 18D1 light chain (Fig.…”

Blocking TWEAK-Fn14 interaction inhibits hematopoietic stem cell transplantation-induced intestinal cell death and reduces GVHD

“…Starting on day 1 posttransplantation, mice were treated with an ADCC-defective (18D1-dead) and an ADCC-enhanced (18D1-enhanced) variant of 18D1, as well as with an irrelevant hIgG1 control antibody. 22 Treatment of mice with the 18D1-dead antibody resulted in significantly prolonged survival compared with transplanted mice treated with the control hIgG1, whereas 18D1-enhanced had no effect (median survival: hIgG, 8 days; 18D1-enhanced, 8 days; 18D1-dead, .30 days) ( Figure 1B). Mice receiving 18D1-dead after allo-HCT initially lost as much weight as did control hIgG1-treated mice, but recovered from allo-HCT by day 9 after transplantation ( Figure 1C).…”

“…This llama-derived antibody efficiently blocks TWEAK binding to human and murine Fn14. 22 When expressed as a human IgG1, 18D1 elicits a strong inhibitory effect on soluble and membrane TWEAKinduced Fn14 signaling. However, like other Fn14-specific hIgG1 For personal use only.…”

“…22 Rituximab, a therapeutic human IgG1 antibody recognizing human but not murine CD20, was purchased from Hoffmann La-Roche (Basel, Switzerland). Balb/c and C57Bl/6 (B6) mice were purchased from Charles River (Sulzfeld, Germany).…”