Inhibition of human renal cancer by monoclonal-anti-body-linked methotrexate in an ascites tumor model.
The monoclonal antibody DAL K29 against a cell-surface antigen associated with a human renal cell carcinoma was covalently linked to the antifolate methotrexate with full retention of antibody activity and partial retention of drug activity. Using an ascites tumor model, developed after intraperitoneal (i.p.) inoculation of 5 x 10(6) cells of the human kidney cancer line Caki-1 per pristane-primed nude mouse, we showed that the methotrexate-Dal-K29 conjugate was a more potent tumor inhibitor (P less than 0.0005) of human renal cell carcinoma (which is resistant to currently available modalities including chemotherapy) than the drug or mAb alone, the drug linked to an isotype-matched nontumor-specific IgG or a mixture of the drug and the mAb. Only the conjugate could produce tumor-free survival in a proportion of the mice during the period of observation (i.e. 150 days after tumor inoculation).
Singh
M
M
Department of Pharmacy, Dalhousie University, Halifax, Nova Scotia, Canada.
Ghose
T
T
Kralovec
J
J
Blair
A H
AH
Belitsky
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D000922:Immunotoxins / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D000922:Immunotoxins; D008727:Methotrexate