Preparation of antigastric cancer monoclonal antibody MGb2-mitomycin C conjugate with improved antitumor activity.
In the present study, an antigastric cancer monoclonal antibody, MGb2, was chosen to prepare antibody-mitomycin C conjugate with dextran T-40 as intermediary. Up to 20 molecules of mitomycin C were specifically bound per molecule of antibody, without significantly impairing the antigen-binding capacity of the antibody and the pharmacological activity of mitomycin C. The conjugate showed selective cytotoxicity upon human gastric cancer cell line SGC-7901 in vitro. Radioimmunoimaging and biodistribution studies indicated that, after conjugation with mitomycin C via dextran T-40 as intermediary, the tumor localization capacity of the antibody was well-retained. When tested in nude mice inoculated with human gastric carcinoma GAII in bilateral subrenal capsules, intraperitoneal injection of the conjugate twice a week for 3 weeks at the dose of 1 mg/kg of drug gave a tumor inhibitory rate of 152.29%, the result being far better than that of free mitomycin C or an irrelevant conjugate. A similar result was found in another nude mouse model of human gastric carcinoma SGC-7901. Meanwhile, after conjugation with antibody, the toxicity of mitomycin C on tested animals was significantly reduced.
Li
S
S
Laboratory of Gastroenterology, Xijing Hospital, Xi'an, Shaanxi Province, China.
Zhang
X Y
XY
Zhang
S Y
SY
Chen
X T
XT
Chen
L J
LJ
Shu
Y H
YH
Zhang
J L
JL
Fan
D M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004355:Drug Stability; D006801:Humans; D000922:Immunotoxins / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000922:Immunotoxins; D008937:Mitomycins; D016685:Mitomycin