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.
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.
Lorberboum-Galski
H
H
Division of Cancer Biology and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Lafyatis
R
R
Case
J P
JP
FitzGerald
D
D
Wilder
R L
RL
Pastan
I
I
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
D005098:Exotoxins; C057961:IL-2-PE40 chimeric protein, recombinant; D007166:Immunosuppressive Agents; D000922:Immunotoxins; D007376:Interleukin-2; D011994:Recombinant Proteins; D009243:NAD