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Sensitivity and Selectivity of Ricin Toxin A Chain-Monoclonal Antibody 791T/36 Conjugates against Human Tumor Cell Lines

Cancer Research Campaign Laboratories, University of Nottingham, Nottingham NG7 2RD, United Kingdom [M. J. E., N. W. B., R. W. B.] and The XOMA Corporation, Berkeley, California 94710 [V. S. B., H. M. L., P. S.]

Ricin toxin A chain (RTA) was conjugated to monoclonal antibody 791T/36, which was raised originally against human osteogenic sarcoma cell line 791T. The resultant conjugates were characterized and tested for cytotoxicity against a panel of human tumor cell lines representing a defined range of antigenicity with regard to 791T/36. Conjugates were highly cytotoxic for cells expressing high antigen density, inhibiting cell survival at RTA concentrations three to four orders of magnitude lower than that possible with RTA alone. Cytotoxicity of conjugates diminished with decreasing 791T/36 antigen concentration on target cells, but significant effects were seen against cells of low or intermediate antigenicity. Cytotoxicity could be blocked specifically by excess 791T/36 antibody, clearly indicating that antigen binding was a necessary part of the mechanism of action. Comparison with drug-antibody conjugates indicated that RTA immunotoxins are much more active, but discriminate less readily than drug-antibody conjugates between cells of different antigenicity. It is suggested that these properties be taken into account with regard to practical application and future development.

¹ Supported by the Cancer Research Campaign, London, United Kingdom.

Received 2/24/86. Revised 7/11/86. Accepted 7/29/86.

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