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Antitumor Activity of an Immunotoxin in a Nude Mouse Model of Human Ovarian Cancer

Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892 [D. J. F., M. C. W., I. P.]; Cetus Corporation, Emeryville, California 94608 [M. J. B., R. J. F., J. L. W., A. E. F.]; and Medicine Branch, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, Maryland 20892 [T. C. H., R. F. O.]

An immunotoxin composed of an antibody to the human transferrin receptor (454A12) and ricin A chain (RTA) was shown to inhibit the growth of NIH:OVCAR-3 tumors in a nude mouse model of human ovarian cancer. Inhibition of tumor growth by 454A12-RTA was related to the dose administered. The antitumor activity of the immunotoxin was blocked by coinjection of excess antibody with immunotoxin. An immunotoxin made using 454A12 and recombinant ricin A chain (rRTA) had an activity similar to that made with native RTA. The administration of 10 µg or greater of the immunotoxin 454A12-RTA/rRTA had significant antitumor activity. The injection of 30 µg of an irrelevant immunotoxin, MOPC21-RTA, or 30 to 500 µg of the 454A12 antibody had no antitumor activity.

¹ Present address: Department of Medicine, Duke University Medical Center, Durham, NC 27710.

Received 5/12/86. Revised 10/23/86. Accepted 12/ 3/86.

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				I Pastan and D FitzGerald Recombinant toxins for cancer treatment Science, November 22, 1991; 254(5035): 1173 - 1177. [Abstract] [PDF]