THE ANTITUMOR DFFECT OF ADRIAMYCIN CONJUGATED WITH MONOCLONAL ANTIBODY AGAINST GASTRIC CANCER IN VITRO AND IN VIVO
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Abstract
Adriamycin (ADM), an anthracycline cytotoxic agent ,wasconjugatedwith monoclonal antibody 3H11 against gastric cancer via the dextran bridge method.The conjugate 3H11- DEX- ADM, with.molar ratio of 3H11 to ADM being 1:73, re-tained antibody activity to 86%. In the cytotoxicity assay, 3H11-DEX-ADM wasshown to exhibit increased cytotoxicity against the target cell line BGC 823. Its IC50 was 3.75 fold less than that of free ADM. The antitumor effect of the conjugate was evaluated in tumor-bearing nude mice.The results indicate that the specific antibody conjugate .3H11-DEX-ADM cansignificantly inhibit the tumor growth. At the dosage level used in the presentstudy (5μg/mouse ×6 ), 3H11-DEX-ADM showed an inhibition rate of 51.5% ,whereas only moderate inhibition rates were observed with free ADM and the control cornjugate NIgG - DEX- ADM. In addition, experiment was performed to evaluate the combined cytotoxicity of3H11 - DEX- ADM and the conjugate of mitomycin C(3H11 - HSA - MMC) at dif-ferent ratios. It was shown that the combination has no synergistic effect when theirIC50 was compared with that of the two conjugates used alone. The same result was ob-served on combinations of the two corresponding free drugs.
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