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Selective Killing of Human Bladder Cancer Cells by Combined Treatment with A and B Chain Ricin Antibody Conjugates¹

Urologische Universitätsklinik, Universitätskrankenhaus Eppendorf (UKE), Universität Hamburg, 2000 Hamburg 20, Federal Republic of Germany

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.

¹ This work was supported by Deutsche Krebshilfe.

² To whom requests for reprints should be addressed, at EMBL, Meyerhofstr. 1, 6900 Heidelberg, Federal Republic of Germany.

Received 4/ 8/86. Revised 7/24/86. Accepted 10/ 2/86.

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