Bispecific antibody targeting of doxorubicin to carcinoembryonic antigen-expressing colon cancer cell lines in vitro and in vivo

A bispecific monoclonal antibody (BsMAb) recognising carcinoembryonic antig en (CEA) and doxorubicin (Dox) was used in colorimetric microcytotoxicity a ssays with 3 human colon cancer cell lines (COLO320DM, SKCOI and LS174T) sh owing no, high or medium CEA expression, respectively, The IC50 values for Dox with COLO320DM, SKCOI and LS174T were 1,163, 28.5 and 324 ng/ml, respec tively. BsMAb caused statistically significant reductions in Dox IC50 value s at I, 0.1 and 0.01 mug/ml with the CEA-expressing cell lines SKCOI and LS 174T but not with COLO320DM, BsMAb or control antibody alone had no signifi cant effect on the cell viability of any of the cell lines and did not redu ce Dox IC50 values, In vivo, there was a statistically significant inhibiti on of the growth of CEA-expressing LS174T cells growing as xenografts in nu de mice treated with BsMAb and Dox compared to control mice, This effect wa s not seen with COLO320DM xenografts, Our results demonstrate that a BsMAb that recognises CEA and Dox can reduce the IC50 for Dox in vitro and inhibi t growth in vivo in a CEA-specific manner, (C) 2001 Wiley-Liss, Inc.