Developing a New Generation of TNFα Antagonists for the Treatment of Rheumatoid Arthritis

Generation of the receptor–immunoglobulin fusion protein Enbrel^®. Sequences coding for the p75 TNF receptor extracellular domain, cloned from a human cDNA library, are inserted into a plasmid vector containing the CH2 and CH3 heavy chain constant domain sequences and subsequently transfected into Chinese hamster ovary cells. These cells secrete a homodimeric fusion protein because of the interchain disulfide links between the two CH2 domains.