MedImmune公司研制出治疗哮喘的白介素9单克隆抗体

一项最新研究证实IL9调节肥大细胞，这种细胞释放介质导致气管或者支气管气道收缩。这种气道超敏（AHR）损害气流进入肺部，这项研究结果可以用于研制开发哮喘治疗的新药物。

2005年5月在美国圣地亚哥举行的美国胸科学会年会上，来自MedImmune的研究人员报道了这些研究结果。他们的数据证实：IL9对AHR的作用，依赖于肥大细胞的增殖和成熟。在该项研究中，肥大细胞的过度表达与肺部两种高水平的介质有关：半胱氨酰白三烯(CystLTs)和前列腺素E2 (PGE2)，已经知道这些介质能够直接作用于平滑肌细胞，与内源性气道张力的改变有关，表现为AHR。

IL9与哮喘症状有关，包括黏液分泌、肺部炎症细胞浸润、以及IgE的生成。MedImmune正在评估IL9单克隆抗体治疗或者预防症状性、中度~重度、持续性哮喘。该公司已经在健康受试者完成了该公司的抗IL9单克隆抗体的I期剂量梯度探索、静脉注射临床试验。下一步，该公司计划开始皮下注射给药的II期临床剂量探索试验。

MedImmune公司的研究部高级主任Anthony Coyle博士说：“我们期望研制开发出阻断IL9的抗体治疗方法，这可能减少肥大细胞来源的与哮喘以及其他疾病相关的因子。”

MAbs to Target IL-9 in Asthma
 
A new study has demonstrated that interleukin-9 (IL-9) regulates mast cells, which release mediators that cause the bronchi or bronchial airway to constrict. This airway hyperreactivity (AHR) impairs airflow into the lungs, a finding being used to develop a new therapy for asthma.

The findings were presented at the annual meeting of the American Thoracic Society in San Diego (CA, USA) in May 2005 by researchers from MedImmune, Inc. (Gaithersburg, MD, USA). Their data demonstrated that IL-9’s effect on AHR depended on the proliferation and maturation of mast cells. In the study, overexpression of mast cells was associated with high lung levels of two mediators: cysteinyl leukotrienes (CystLTs) and prostaglandin E2 (PGE2), which are known to have direct effects on smooth muscle and have been previously associated with changes in intrinsic airway tone, manifesting as AHR.

IL-9 has been associated with symptoms of asthma, including mucous production, lung infiltration of inflammatory cells, and IgE production. MedImmune is evaluating the potential of monoclonal antibodies (MAbs) targeting IL-9 to treat or prevent symptomatic, moderate-to-severe, persistent asthma. The company has already completed a phase I dose-escalation, intravenously administered study in healthy adults with its lead anti-IL-9 MAb. Next, it plans to initiate a subcutaneously administered phase II dose-escalation study.

“We look forward to advancing the development of antibody therapies to block IL-9, which may have the potential to reduce mast cell-derived respiratory factors associated with asthma and other illnesses,” observed Anthony Coyle, Ph.D., senior director, research, at MedImmune.