RECOMBINANT PSEUDOMONAS EXOTOXIN: CONSTRUCTION OF AN ACTIVE IMMUNOTOXIN WITH LOW SIDE EFFECTS

摘要

Large amounts of various modified forms of Pseudomonasexotoxin are produced. At least one of the modified forms (pJH8)of the exotoxin exhibits low toxicity to human or mouse cells byitself but retains its enzymatic activity and makes a very activecell specific immunotoxin with very low nonspecific cytotoxicity.All the constructs with low cytotoxic activity will be useful asvaccines to produce the antibodies to treat pseudomonas sepsis.In addition, the protein encoded by domain I alone could beadministered directly to patients to treat pseudomonas sepsisbecause that domain would block toxin binding to cells. Clonescontaining domain II and particularly clone pJH12 can be fused toother toxins which have low activity (such as ricin A chain orpokeweed antiviral protein) to increase cell-killing activitywithout increasing their nonspecific binding to cells.