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 antigen (CEA) and doxorubicin (Dox) was used in colorimetric microcytotoxicity assays with 3 human colon cancer cell lines (COLO320DM, SKCO1 and LS174T) showing no, high or medium CEA expression, respectively. The IC50 values for Dox with COLO320DM, SKCO1 and LS174T were 1,163, 28.5 and 324 ng/ml, respectively. BsMAb caused statistically significant reductions in Dox IC50 values at 1, 0.1 and 0.01 microg/ml with the CEA-expressing cell lines SKCO1 and LS174T but not with COLO320DM. BsMAb or control antibody alone had no significant effect on the cell viability of any of the cell lines and did not reduce Dox IC50 values. In vivo, there was a statistically significant inhibition of the growth of CEA-expressing LS174T cells growing as xenografts in nude mice treated with BsMAb and Dox compared to control mice. This effect was 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 inhibit growth in vivo in a CEA-specific manner.
Ford
C H
CH
Department of Surgery, Faculty of Medicine, Kuwait University, Safat, Kuwait. ford@hsc.kuniv.edu.kw
Osborne
P A
PA
Rego
B G
BG
Mathew
A
A
D000818:Animals; D018033:Antibodies, Bispecific / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis*; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism*; D004396:Coloring Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D000970:Antineoplastic Agents; D002272:Carcinoembryonic Antigen; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D004317:Doxorubicin; C022616:thiazolyl blue