Inhibition of human renal cancer by monoclonal antibody targeted methotrexate-containing liposomes in an ascites tumor model.
The monoclonal antibody DAL K29 against a human renal cell carcinoma associated cell surface antigen was covalently linked to small unilamellar lipid vesicles (SUV) containing the antifolate, methotrexate (MTX), with full retention of antibody activity. In an ascites tumor model developed after intraperitoneal inoculation of 5 x 10(6) cells of the human kidney cancer line Caki-1 per pristane primed nude mouse, the DAL K29 linked MTX-containing SUV was a more potent tumor inhibitor (P less than 0.0005) than the drug or MAB alone, MTX-containing SUV, a mixture of DAL K29 and MTX-containing SUV or MTX-containing SUV linked to an isotype matched nontumor specific IgG.
Singh
M
M
School of Pharmacy, Dalhousie University, Halifax, Nova Scotia, Canada.
Ghose
T
T
Mezei
M
M
Belitsky
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology; D002460:Cell Line; D004337:Drug Carriers; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008081:Liposomes; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D004337:Drug Carriers; D008081:Liposomes; D008727:Methotrexate