[The antitumor effect of adriamycin conjugated with monoclonal antibody against gastric cancer in vitro and in vivo].
Adriamycin (ADM), an anthracycline cytotoxic agent, was conjugated with 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, retained antibody activity to 86%. In the cytotoxicity assay, 3H11-DEX-ADM was shown 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 can significantly inhibit the tumor growth. At the dosage level used in the present study (5 micrograms/mouse x 6), 3H11-DEX-ADM showed an inhibition rate of 51.5%, whereas only moderate inhibition rates were observed with free ADM and the control conjugate NIgG-DEX-ADM. In addition, experiment was performed to evaluate the combined cytotoxicity of 3H11-DEX-ADM and the conjugate of mitomycin C (3H11-HSA-MMC) at different ratios. It was shown that the combination has no synergistic effect when their IC50 was compared with that of the two conjugates used alone. The same result was observed on combinations of the two corresponding free drugs.
Zhang
Y T
YT
Bejing Institute for Cancer Research.
Wang
N Q
NQ
Li
N
N
Liu
T
T
Dong
Z W
ZW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use*; D000922:Immunotoxins / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D016685:Mitomycin; D004317:Doxorubicin