SPECIFIC KILLING OF LYMPHOMA-CELLS BY CYTOTOXIC T-CELLS MEDIATED BY ABISPECIFIC DIABODY

Antibody fragments produced by bacterial fermentation lack natural eff ector functions, Bispecific antibody fragments, however, can be endowe d with effector functions, for example cell-mediated killing, by bindi ng to and retargeting of cytotoxic cells, Diabodies are a class of eng ineered antibody fragments with two antigen binding sites, consisting of two associated chains; each chain consists of heavy and light chain variable domains linked by a short polypeptide linker, In contrast to IgG, or other antibody fragments in which the two binding sites can t ake up a range of orientations and spacings, the diabody structure is more rigid and compact, with the two binding sites separated by 65 Ang strom (less than half the distance in IgG), To establish whether diabo dies could also be used in cell-mediated killing, we have explored the use of a bispecific diabody binding to an idiotypic marker on mouse B -cell lymphoma (BCL-1) and to mouse CD3, The bispecific diabody activa ted naive T-cells and also mediated the specific killing of the lympho ma cells by cytotoxic T-cells, The diabody was less active in T-cell a ctivation but 10-fold more active (w/v) in killing than an analogous b ispecific IgG.