RETARGETING SERUM IMMUNOGLOBULIN WITH BISPECIFIC DIABODIES

Monospecific antibody fragments produced in bacteria lack the Fc porti on of antibodies, and are therefore unable to recruit natural effector functions. We describe the use of a bispecific antibody fragment (dia body) to recruit the whole spectrum of antibody effector functions by retargeting serum immunoglobulin (Ig). One arm of the diabody was dire cted against the target antigen, and the other against the serum Ig. T he bispecific diabodies were able to recruit complement, induce mononu clear phagocyte respiratory burst and phagocytosis, and promote synerg istic cytotoxicity towards colon carcinoma cells in conjunction with C D8(+) T-cells, Further, by virtue of binding to serum Ig their half-li fe (beta-phase) was increased fivefold compared to a control diabody o f the same molecular weight. Such bispecific diabodies may provide an attractive alternative to monoclonal antibodies for serotherapy.