Ford C H, Osborne P A, Rego B G, Mathew A
Department of Surgery, Faculty of Medicine, Kuwait University, Safat, Kuwait.
Int J Cancer. 2001 Jun 15;92(6):851-5. doi: 10.1002/ijc.1262.
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.
一种识别癌胚抗原（CEA）和阿霉素（Dox）的双特异性单克隆抗体（BsMAb）用于比色微细胞毒性试验，该试验采用了3种人结肠癌细胞系（COLO320DM、SKCO1和LS174T），它们分别不表达CEA、高表达CEA或中等表达CEA。Dox对COLO320DM、SKCO1和LS174T的IC50值分别为1163、28.5和324 ng/ml。BsMAb在1、0.1和0.01 μg/ml时，使表达CEA的细胞系SKCO1和LS174T的Dox IC50值有统计学意义的降低，但对COLO320DM无此作用。单独的BsMAb或对照抗体对任何细胞系的细胞活力均无显著影响，也未降低Dox的IC50值。在体内，与对照小鼠相比，在用BsMAb和Dox处理的裸鼠中，作为异种移植物生长的表达CEA的LS174T细胞的生长受到统计学显著抑制。COLO320DM异种移植物未观察到这种效应。我们的结果表明，一种识别CEA和Dox的BsMAb可在体外降低Dox的IC50，并以CEA特异性方式在体内抑制生长。
