Ozmen L, Fountoulakis M, Gentz R, Garotta G
Hoffmann-La Roche Ltd., CH-4002 Basel, Switzerland.
Int Rev Exp Pathol. 1993;34 Pt B:137-47. doi: 10.1016/b978-0-12-364935-5.50014-6.
Several in vivo experiments support the hypothesis that an IFN-gamma antagonist may have therapeutic applications in autoimmune diseases, hypersensitivities, and alloreactions. IFN-gamma exerts its biological activity through the binding to a single-chain cell surface receptor. The protein that corresponds to the external domain of mouse IFN-gamma receptor was expressed in insect cells infected with recombinant baculovirus; this protein was characterized and used in vivo as a prototype of the IFN-gamma antagonist. This protein does not show any strong antigenicity after in vivo injection in mice. Despite a blood half-life of only 1-3 hr as demonstrated in pharmacokinetic experiments, the mouse soluble IFN-gamma R was able to modify the onset of acute GVHD (alloreaction) and chronic GVHD (lupuslike disease).
多项体内实验支持这样一种假说,即γ干扰素拮抗剂可能在自身免疫性疾病、超敏反应和同种异体反应中具有治疗应用。γ干扰素通过与单链细胞表面受体结合发挥其生物学活性。与小鼠γ干扰素受体胞外结构域相对应的蛋白质在感染重组杆状病毒的昆虫细胞中表达;对该蛋白质进行了表征,并在体内用作γ干扰素拮抗剂的原型。该蛋白质在小鼠体内注射后未表现出任何强抗原性。尽管药代动力学实验表明其血液半衰期仅为1 - 3小时,但小鼠可溶性γ干扰素受体能够改变急性移植物抗宿主病(同种异体反应)和慢性移植物抗宿主病(狼疮样疾病)的发病情况。