Antitumor Effects of Interleukin ^-Pseudomonas Exotoxin Chimeric Molecules against the Human Hepatocellular Carcinoma, PLC/PRF/5 in Mice

IL6-PE40 and IL6-PE664G'" are chimeric molecules composed of interleukin 6 (11.6) fused to a truncated form (PE40) or a full-length mutated form (PE664GI")of Pseudomonas exotoxin. Both forms of IL6Pseudomonas exotoxin are cytotoxic to IL6 receptor-bearing tumor cell types in culture. In this report, we show that both IL6-PE40 and IL6I'l .(•><>"''" 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-PE664(;|Ushowed improved ther apeutic 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 \\A-Pseudomonas exotoxin can suppress the growth of cancer which overexpresses cell surface IL6 receptors.