Bispecific human IgG by design

A major obstacle facing the development of bispecific antibodies as therapeutics has been the formidable task of producing these complex molecules in sufficient quantity and purity for clinical trials. These production difficulties have been largely overcome with the advent of efficient methods for the secretion of designer bispecific antibody fragments such as diabodies and miniantibodies from Escherichia coli. In contrast, the creation of bispecific IgG by the coexpression of two different IgG is highly inefficient due to unwanted pairings of the component heavy and light chains. A robust technology for the creation of bispecific IgG has recently been developed that virtually precludes IgG contaminants, as reviewed here. This technology is anticipated to spur the clinical development of bispecific IgG and other bifunctional Fc-containing molecules such as antibody/immunoadhesin hybrids and bispecific immunoadhesins.