Enhanced antitumor activity of daunomycin conjugated with antigastric cancer monoclonal antibody MGb2.
In the present study, an antigastric cancer monoclonal antibody, MGb2, was chosen to prepare an antibody-daunomycin conjugate. Daunomycin was modified by cis-aconitic anhydride, and the derivative was linked to antibody, a carbodiimide reagent being used to produce peptide bonding. Four to five molecules of daunomycin were specifically bound per molecule of antibody, without severely impairing the pharmacological activity of daunomycin and with minimal loss of antibody activity. A tetrazolium dye colorimetric assay indicated that the MGb2-daunomycin conjugate exhibited selective cytotoxicity against human gastric cancer cells SGC-7901 in vitro. The tumor localization in BALB/c nude mice showed that the specific conjugate could recognize the tumor as efficiently as the unconjugated antibody. MGb2-daunomycin conjugate could significantly suppress the growth of human gastric carcinoma GAII inoculated under the renal capsules of BALB/c nude mice. Intraperitoneal injection of MGb2-daunomycin conjugate twice a week for 3 weeks at a dose of 1 mg/kg of drug gave a tumor inhibition rate of 91.58%, far more effective than free daunomycin or an irrelevant conjugate.
Li
S
S
Laboratory of Gastroenterology, Xijing Hospital, Shaanxi, China.
Zhang
X Y
XY
Qiao
T D
TD
Chen
X T
XT
Zhang
S Y
SY
Chen
L J
LJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D003630:Daunorubicin / Q000008:administration & dosage*; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000276:immunology; D016019:Survival Analysis; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000922:Immunotoxins; D003630:Daunorubicin