Abstract
Using carboxymethyl dextran (CMdex) as the intermediate drugcarrier, carboplatin (2 cis-diammin platin II, CBDCA : Bristol-Myers-Squibb) was conjugated to anti-CEA monoclonal antibody (MoAb : 1B2)with bridging agents 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide and N-hydroxy-succinimide. MoAb and CMdex were mixed in the molar ratios of from 1 : 1 through 1 : 3000, but CMdex/CBDCA ratios were fixed at 1 : 100 in molar. The conjugation efficiency by this method was that when initially mixed molar ratio of carboplatin to MoAb was more than 10000, 80% of given carboplatin was found to be coupled to MoAb-CMdex, and maximally 626 mg of carboplatin could be conjugated to 1 mg of MoAb. The cytotoxicity and immunoreactivity of the immunoconjugates were evaluated by colony formation method, and by an enzyme immunoassay using Ag-coated beads, respec tively. The cytotoxicity of the immuno-conjugates was dependent only on the drug concentration, equal to that of unconjugated drug, and irrespective to the CBDCA/MoAb ratio. The immuno-reactivity of the conjugates was found no remarkable decrease in comparison with unconjugated antibody. Then we conclude that this conjugation method might be of use, at least significant on the conjugation of carboplatin to monoclonal antibodies.
