HIGH AFFINITY AND POTENCY OF THE PEGYLATED FABʼ FRAGMENT CDP870 — A DIRECT COMPARISON WITH OTHER ANTI-TNF AGENTS

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Purpose: CDP870 is a PEGylated Fab' fragment of an anti-TNF monoclonal antibody that has demonstrated efficacy in patients with Crohn's disease and rheumatoid arthritis.1,2 Several other anti-TNF agents have proved effective as treatment for these conditions. The differences in the mechanism of action of these agents are poorly understood. Owing to the variability in assay methods from different laboratories, it has not previously been possible to compare affinity or in vitro potency data. This is the first study to directly compare the affinity and potency of three anti-TNF agents: CDP870, adalimumab (Humira®), and infliximab (Remicade®) in two different assays under comparable conditions. Methods: (1) Affinity for TNF-α, expressed as the equilibrium dissociation constant (KD), was determined by the technique of surface plasmon resonance using a Biacore® 3000 (Biacore International SA, Uppsala, Sweden). (2) Potency (concentration causing 50% inhibition of natural TNF-α activity [IC50]) was measured using the L929 bioassay (a mouse fibroblast cell line killed by TNF-α) in the presence of actinomycin D. Natural TNF-α was produced by a lipopolysaccharide-stimulated human monocyte cell line. Results: Affinity parameters are summarized in the table. CDP870 demonstrated higher affinity for TNF-α than adalimumab and infliximab. Potency data, obtained using natural TNF-α, reflected the affinity data, with CDP870 (IC500.35 ng/mL) more potent than adalimumab and infliximab (IC506 and 5 ng/mL, respectively).TableConclusions: CPD870 was selected to have a very high affinity for TNF-α As a result, despite the fact that CDP870 is a monovalent antibody fragment, its potency is greater than that of the bivalent antibodies adalimumab and infliximab. 1. Schreiber S, et al. AGA 2003. 2. Keystone E, et al. ACR 2001. Data are mean ± SD; (n = 3) except for CDP870 (n = 4). Data based on concentration calculations assuming that TNF-α is monomeric. ka = association rate constant; kd = dissociation rate constant; KD = kd/ka