Selective killing of human bladder cancer cells by combined treatment with A and B chain ricin antibody conjugates.

The monoclonal antibody 486P 3-12-1 raised against transitional bladder carcinoma cells was coupled to either the ricin A or B chain. The toxicity of A chain conjugates could be enhanced by addition of either free ricin B chain or by ricin B chain coupled to 486P 3-12-1 or to antibodies conjugated to ricin B and directed against the mouse monoclonal antibody. Using a two-step procedure where the A and B chains of ricin were delivered separately, the appropriate target cells 486P and 647V were killed, while the pancreatic cell line QGP-1 was not affected. The efficiency of killing by immunotoxin was independent whether free or coupled B chain was used, but B chain was essential for mediating the toxicity of the A chain. The two-step procedure enhances the selectivity of immunotoxin treatment by reducing nonspecific toxicity. Such a procedure could be applicable in vivo by direct administration to the bladder cavity.