A major obstacle facing the development of bispecific antibodies as therape
utics has been the formidable task of producing these complex molecules in
sufficient quantity and purity for clinical trials. These production diffic
ulties have been largely overcome with the advent of efficient methods for
the secretion of designer bispecific antibody fragments such as diabodies a
nd miniantibodies from Escherichia coli. In contrast, the creation of bispe
cific IgG by the coexpression of two different IgG is highly inefficient du
e to unwanted pairings of the component heavy and light chains. A robust te
chnology for the creation of bispecific IgG has recently been developed tha
t virtually precludes IgG contaminants, as reviewed here. This technology i
s anticipated to spur the clinical development of bispecific IgG and other
bifunctional Fc-containing molecules such as antibody/immunoadhesin hybrids
and bispecific immunoadhesins. (C) 2001 Elsevier Science BN. All rights re
served.