Lorberboum-Galski H, Lafyatis R, Case J P, FitzGerald D, Wilder R L, Pastan I
Division of Cancer Biology and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Int J Immunopharmacol. 1991;13(2-3):305-15. doi: 10.1016/0192-0561(91)90112-k.
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.
IL-2-PE40是一种嵌合细胞毒素,由与缺乏结合结构域的截短形式的铜绿假单胞菌外毒素(PE)融合的白细胞介素2(IL-2)组成。已证明,当每天腹腔注射两次时,IL-2-PE40在几种体内模型中表现出治疗效力。在这里,我们表明,通过渗透泵持续给药IL-2-PE40可特异性预防大鼠佐剂诱导的关节炎的发展,与每日重复腹腔注射相比,治疗效果有所改善。通过添加NAD(嵌合毒素酶部分的底物)实现了IL-2-PE40在37摄氏度下的稳定化,以便通过泵持续给药。