Inhibition of human renal cancer by methotrexate linked to a monoclonal antibody.
The monoclonal antibody DAL K29 against a human renal cell carcinoma associated cell surface antigen was covalently linked to the antifolate methotrexate with full retention of antibody reactivity and partial retention of drug activity. In a colony inhibition assay, antibody-conjugated methotrexate was 400% more potent in inhibiting the growth of the human kidney cancer line Caki-1 than equimolar amounts of the free drug. Comparable amounts of the antifolate linked to normal mouse IgG did not inhibit the growth of Caki-1 cells. Furthermore, the methotrexate-DAL K29 conjugate had no effect on the two nontarget human cell lines tested, melanoma M21 and B cell leukemia D10-1 cells, even when the conjugate contained amounts of methotrexate equivalent to the 50% inhibitory concentration of the free drug for the nontarget cell lines or an amount equivalent to the 50% inhibitory concentration of the conjugated drug for Caki-1 cells.
Singh
M
M
College of Pharmacy, Department of Pathology, Dalhousie University, Halifax Scotia, Canada.
Kralovec
J
J
Mezei
M
M
Ghose
T
T
D000911:Antibodies, Monoclonal / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D007680:Kidney Neoplasms / Q000473:pathology*; D008727:Methotrexate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D008727:Methotrexate