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[Cancer Research 51, 2831-2836, June 1, 1991]
© 1991 American Association for Cancer Research
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Antitumor Effects of Interleukin 6-Pseudomonas Exotoxin Chimeric Molecules against the Human Hepatocellular Carcinoma, PLC/PRF/5 in Mice

Clay B. Siegall1, Robert J. Kreitman, David J. FitzGerald and Ira Pastan

Laboratory of Molecular Biology, Division of Cancer Biology, Diagnosis and Centers, National Cancer Institute, NIH, Bethesda, Maryland 20892

IL6-PE40 and IL6-PE664Glu are chimeric molecules composed of interleukin 6 (IL6) fused to a truncated form (PE40) or a full-length mutated form (PE664Glu) of Pseudomonas exotoxin. Both forms of IL6-Pseudomonas exotoxin are cytotoxic to IL6 receptor-bearing tumor cell types in culture. In this report, we show that both IL6-PE40 and IL6-PE664Glu have antitumor activity against the hepatocellular carcinoma PLC/PRF/5 implanted s.c. in nude mice. The PLC/PRF/5 tumor contains about 2300 IL6 receptors per cell. IL6-PE664Glu showed improved therapeutic efficacy when released continuously for 7 days by an osmotic pump planted i.p. than when administered by multiple daily i.p. injections. Both forms of IL6 toxin exhibited a schedule-dependent antitumor effect. These results demonstrate that IL6-Pseudomonas exotoxin can suppress the growth of cancer which overexpresses cell surface IL6 receptors.

1 Present address: Pharmaceutical Research Institute, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492.

Received 2/14/91. Accepted 3/26/91.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1991 by the American Association for Cancer Research.