Antitumor effects of interleukin 6-Pseudomonas exotoxin chimeric molecules against the human hepatocellular carcinoma, PLC/PRF/5 in mice.
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.
Siegall
C B
CB
Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Kreitman
R J
RJ
FitzGerald
D J
DJ
Pastan
I
I
D036002:ADP Ribose Transferases; D000818:Animals; D001426:Bacterial Proteins; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D005098:Exotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology*; D007958:Leukocyte Count; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins; D014407:Tumor Cells, Cultured
D001426:Bacterial Proteins; D005098:Exotoxins; C064195:IL-6-PE40 protein, chimeric; D015850:Interleukin-6; D011993:Recombinant Fusion Proteins; C068846:interleukin-6-PE66(4Glu) chimeric protein, recombinant; D036002:ADP Ribose Transferases