title: Administration of IL-2-PE40 via osmotic pumps prevents adjuvant induced arthritis in rats. Improved therapeutic index of IL-2-PE40 administered by continuous infusion.
abstract: IL-2-PE40 is a chimeric cytotoxin composed of interleukin 2 (IL-2) fused to a truncated form of Pseudomonas exotoxin (PE) that lacks its binding domain. IL-2-PE40 has been shown to exhibit therapeutic potency in several models in vivo when administered i.p. twice a day. Here we show that the continuous administration of IL-2-PE40 by an osmotic pump specifically prevents the development of adjuvant induced arthritis in rats with an improved therapeutic efficacy as compared to daily repeated i.p. injections. Stabilization of IL-2-PE40 at 37 degrees C for the continuous administration by pumps was achieved by adding NAD, the substrate for the enzyme portion of the chimeric toxin.
authors.affiliation: Division of Cancer Biology and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: H
authors.initials: H
authors.lastname: Lorberboum-Galski
authors.forename: R
authors.initials: R
authors.lastname: Lafyatis
authors.forename: J P
authors.initials: JP
authors.lastname: Case
authors.forename: D
authors.initials: D
authors.lastname: FitzGerald
authors.forename: R L
authors.initials: RL
authors.lastname: Wilder
authors.forename: I
authors.initials: I
authors.lastname: Pastan
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000517:prevention & control*; D004355:Drug Stability; D005098:Exotoxins / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D000922:Immunotoxins / Q000008:administration & dosage* / Q000097:blood; D015918:Infusion Pumps, Implantable; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000097:blood; D009243:NAD / Q000008:administration & dosage; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins; D013696:Temperature
chemical_list: D005098:Exotoxins; C057961:IL-2-PE40 chimeric protein, recombinant; D007166:Immunosuppressive Agents; D000922:Immunotoxins; D007376:Interleukin-2; D011994:Recombinant Proteins; D009243:NAD