Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University, School of Medicine, New Haven, CT 06520-8063, USA.
Am J Pathol. 2010 Feb;176(2):1050-6. doi: 10.2353/ajpath.2010.090757. Epub 2009 Dec 30.
Endometriosis is a major cause of chronic pain, infertility, medical and surgical interventions, and health care expenditures. Tissue factor (TF), the primary initiator of coagulation and a modulator of angiogenesis, is not normally expressed by the endothelium; however, prior studies have demonstrated that both blood vessels in solid tumors and choroidal tissue in macular degeneration express endothelial TF. The present study describes the anomalous expression of TF by endothelial cells in endometriotic lesions. The immunoconjugate molecule (Icon), which binds with high affinity and specificity to this aberrant endothelial TF, has been shown to induce a cytolytic immune response that eradicates tumor and choroidal blood vessels. Using an athymic mouse model of endometriosis, we now report that Icon largely destroys endometriotic implants by vascular disruption without apparent toxicity, reduced fertility, or subsequent teratogenic effects. Unlike antiangiogenic treatments that can only target developing angiogenesis, Icon eliminates pre-existing pathological vessels. Thus, Icon could serve as a novel, nontoxic, fertility-preserving, and effective treatment for endometriosis.
子宫内膜异位症是慢性疼痛、不孕、医疗和手术干预以及医疗支出的主要原因。组织因子（TF）是凝血的主要启动因子，也是血管生成的调节剂，通常内皮细胞不表达；然而，先前的研究表明，实体瘤中的血管和黄斑变性中的脉络膜组织都表达内皮 TF。本研究描述了子宫内膜异位症病变中内皮细胞异常表达 TF。免疫缀合物分子（Icon）与这种异常的内皮 TF 具有高亲和力和特异性结合，已被证明能诱导细胞溶解免疫反应，从而根除肿瘤和脉络膜血管。使用子宫内膜异位症的无胸腺小鼠模型，我们现在报告说，Icon 通过血管破坏在没有明显毒性、降低生育能力或随后的致畸作用的情况下，很大程度上破坏了子宫内膜异位症的植入物。与只能靶向新生血管生成的抗血管生成治疗不同，Icon 消除了预先存在的病理性血管。因此，Icon 可以作为一种新型的、无毒的、保留生育能力的、有效的子宫内膜异位症治疗方法。
