The Challenge of Monoclonal Antibody Drugs

This chapter discusses the efforts to develop monoclonal antibody (Mab) therapeutics. The quick commercialization of Mab diagnostics prompted many to assume that Mab therapeutics would soon reach the market. These high expectations were given a boost in June 1986 when the FDA approved Ortho Diagnostic Systems' Orthoclone (muromonab-CD3) in order to prevent kidney rejection in transplant patients. Orthoclone was the first Mab approved anywhere for use as a drug in humans. Yet Orthoclone was not without problems. Between 5 and 10 percent of patients on it experienced significant side effects, including fevers, thromboses, and anaphylactic shock. Other Mab therapies tested in this period also led to complications. Part of the problem was that the antibodies were derived from mice or rats, which the human immune system treated as foreign and attacked. Such antibodies also only survived for between fifteen and thirty hours in humans, so the drugs had to be infused in high and frequent doses. Moreover, their recognition of human receptors was poor.