FIVE DOSE TRIAL OF ABX IL8 IN TREATMENT OF SEVERE PLAQUE PSORIASIS

ABX-IL-8是在转基因小鼠体内产生的人源化单抗。该抗体对IL-8有很高的亲和力，并能中和IL-8，如几种检测系统所证明的那样。该抗体抑制与中性粒细胞的结合，抑制IL-8诱导的钙流动，并抑制MAC-1的表达、弹性酶释放和趋化。克鲁格博士通过在一个实验系统中证明，当注射IL-8时，来自牛皮癣患者的未受影响的皮肤移植到裸鼠身上，会产生类似牛皮癣的皮损，从而完成了这一方案的开发工作。给予ABX-IL-8可完全阻断这一作用。这些动物数据表明，针对IL-8的抗体可能是治疗斑块期牛皮癣的有效方法。通过对GCRC进行的研究，确定了该药物的安全性，然后确定了适当的剂量范围。事实证明，这种药物在治疗斑块期牛皮癣方面非常有效，目前正在准备一份描述这种疗法的有益效果的手稿。

ABX-IL-8 is a humanized monoclonal antibody generated in transgenic mice. The antibody has a high affinity for IL-8, and can neutralize IL-8, as demonstrated in several assay systems. The antibody inhibits binding to neutrophils, inhibits IL-8-induced calcium flux, and inhibits MAC-1 expression, elastase release, and chemotaxis. Dr. Krueger did the developmental work for this protocol by demonstrating in an experimental system that unaffected skin from patients with psoriasis, grafted onto nude mice, generated psoriasis-like lesions when IL-8 was injected. This effect was totally blocked by administering ABX-IL-8. These animal data suggest that an antibody against IL-8 might be an effective method of treating plaque-phase psoriasis. From the study done on the GCRC, safety of the drug was determined, and then appropriate dosing ranges established. The drug proved remarkably effective in the treatment of plaque-phase psoriasis, and a manuscript describing the beneficial effects of this therapy is now in preparation.