CONCISE REVIEWS OF PEDIATRIC INFECTIOUS DISEASES Monoclonal Antibody Therapeutics and Risk for Infection

The discovery of a method to produce continuous mouse cell lines synthesizing antibodies of predetermined specificity so revolutionized diagnostics and therapeutics that the scientists responsible were awarded a Nobel Prize only 9 years after their publication. The therapeutic application of monoclonal antibodies (MAbs) as “magic bullets” began with the approval of a murine antibody, muromonab (Ortho-Biotech’s “Orthoclone OKT3”) directed against the lymphocyte surface marker CD3. Muromonab is still used as an agent for the treatment of rejection in solid organ transplantation. Some of the side effects observed with the use of murine MAbs are related to sensitization to murine proteins. Technical advances have permitted the development of chimeric, “humanized,” and fully human antibodies, in which the whole amino acid sequence is human. The main advantage of the “humanization” process is that it allows for long-term administration without the development of anti-antibodies. With the development of so many MAbs, a systematic naming system was required to differentiate them (Table 1). Currently, more than twenty MAbs have been approved by the Food and Drug Administration (FDA), and 100 are in development (Table 2). Some therapeutic antibodies are administered intact, and some are conjugated to radioisotopes or toxins for use as antineoplastic agents. Many MAbs act as immunomodulators (in transplantation and for autoimmune conditions), as antineoplastic agents, or as both. In this review, we summarized the infectious complications that have been reported with these agents, and with selected related, non-MAb immunomodulatory agents. It should be noted that the attribution of a particular complication to an individual drug is difficult for 2 reasons. First, the patient populations that receive MAbs generally are already immunosuppressed and are thus at greater risk of infection. Second, the available clinical trials data often include too few patients to have adequate power to detect rare infections or to distinguish differences in the rates of infections among comparison drugs.