Hufnagel Demetra, Goetz Teddy G, Hu Zhiwei, Nyachieo Atunga, D'Hooghe Thomas, Fazleabas Asgerally, Duleba Antoni, Krikun Graciela, Taylor Hugh S, Lockwood Charles J
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, United States.
Department of Surgery, The Ohio State University College of Medicine, Columbus, OH, United States.
Reprod Biol. 2018 Mar;18(1):109-114. doi: 10.1016/j.repbio.2018.01.009. Epub 2018 Feb 13.
Endometriosis is a common condition in reproductive-aged women characterized by ectopic endometrial lesions of varied appearance, including red, white, blue, black or powder burn coloration, which contribute to chronic pain and infertility. The immunoconjugate molecule (Icon) targets Tissue Factor, a transmembrane receptor for Factor VII/VIIa that is aberrantly expressed in the endothelium supporting ectopic endometrial tissue. Icon has been shown to cause regression of endometriosis in a murine model of disease but prior to this study had not been tested in non-human primates. This study evaluated Icon as a novel treatment for endometriosis in non-human primates (Papio anubis) using an adenoviral vector (AdIcon) delivery system. Female baboons (n = 15) underwent surgical induction of endometriosis. After laparoscopic confirmation of endometriosis lesions 6-weeks post-surgery, the treatment group (n = 7) received weekly intraperitoneal injections of viral particles carrying the sequence for Icon, resulting in expression of the protein, while the control group (n = 8) received no treatment. Icon preferentially reduced the number and volume of red vascularized lesions. Icon may present a novel treatment for endometriosis by degrading red vascularized lesions, likely by targeting tissue factor aberrantly expressed in the lesion vasculature.
子宫内膜异位症是育龄期女性的常见病症，其特征为外观各异的异位子宫内膜病变，包括红色、白色、蓝色、黑色或粉烧伤样颜色，这些病变会导致慢性疼痛和不孕。免疫偶联分子（Icon）靶向组织因子，组织因子是凝血因子VII/VIIa的跨膜受体，在支持异位子宫内膜组织的内皮中异常表达。在疾病的小鼠模型中，Icon已被证明可导致子宫内膜异位症消退，但在本研究之前尚未在非人类灵长类动物中进行测试。本研究使用腺病毒载体（AdIcon）递送系统评估Icon作为非人类灵长类动物（狒狒）子宫内膜异位症的新型治疗方法。雌性狒狒（n = 15）接受了子宫内膜异位症的手术诱导。在术后6周通过腹腔镜确认子宫内膜异位症病变后，治疗组（n = 7）每周接受一次腹腔注射携带Icon序列的病毒颗粒，从而导致该蛋白表达，而对照组（n = 8）不接受治疗。Icon优先减少红色血管化病变的数量和体积。Icon可能通过降解红色血管化病变为子宫内膜异位症提供一种新的治疗方法，可能是通过靶向病变血管中异常表达的组织因子来实现的。
