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 adminstered 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°C for the continuous administration by pumps was achieved by adding NAD, the substrate for the enzyme portion of the chimeric toxin.