Abstract
DAB~486~ILโ2 is a genetically engineered fusion protein consisting of a portion of diphtheria toxin fused to human ILโ2. It is specifically cytotoxic for tumor cells which bear highโaffinity ILโ2 receptors (ILโ2R). DAB~389~ILโ2 is a similarly constructed hybrid protein which is smaller than DAB~486~ILโ2 and is slightly more potent in vitro. We have developed a murine model of ILโ2Rโexpressing malignancy to study the in vivo efficacy of these genetically engineered cytotoxins. Following intravenous administration of CP3 cells, C57BL/6 mice develop tumors which are lymphatic in distribution. When mice are injected i.v. with 10^6^ CP3 cells, 90% of the animals show signs of observable tumor by day 10 to 20; death occurs in 50% of untreated animals by day 30. Intravenous treatment of mice with DAB~486~ILโ2 (10 ฮผg daily for 10 days), beginning 24 hr after administration of CP3 cells, increases mean survival time by approximately 50%. In comparative studies, DAB^389^ILโ2 is more potent in vivo than DAB~486~ILโ2, with approximately 90% of treated animals with no evidence of tumor at 60 days. The mechanism of action of tumor inhibition by DAB~486~ILโ2 is specific, since treatment of animals which have 1Lโ2Rโnegative EL4 tumors has not resulted in increased survival time. In addition, treatment of such tumors with DA~glu53~B~486~ILโ2, a fusion protein which can bind to the ILโ2R but is incapable of inhibiting protein synthesis, is ineffective.