Icon immunoconjugate treatment results in regression of red lesions in a non-human primate (Papio anubis) model of endometriosis

被引:9
|
作者
Hufnagel, Demetra [1 ]
Goetz, Laura G. [1 ]
Hu, Zhiwei [2 ]
Nyachieo, Atunga [3 ]
D'Hooghe, Thomas [4 ]
Fazleabas, Asgerally [5 ]
Duleba, Antoni [6 ]
Krikun, Graciela [1 ]
Taylor, Hugh S. [1 ]
Lockwood, Charles J. [7 ]
机构
[1] Yale Sch Med, Dept Obstet Gynecol &Reprod Sci, New Haven, CT 06520 USA
[2] Ohio State Univ, Coll Med, Dept Surg, Columbus, OH 43210 USA
[3] Inst Primate Res, Dept Reprod Hlth & Noncommunicable Dis, Nairobi, Kenya
[4] KU Leuven Univ Leuven, Dept Dev & Regenerat, Grp Biomed Sci, Campus Gasthuisberg, Leuven, Belgium
[5] Michigan State Univ, Dept Obstet Gynecol & Reprod Biol, Grand Rapids, MI USA
[6] Univ Calif San Diego, Dept Reprod Med, San Diego, CA USA
[7] Univ S Florida, Dept Obstet & Gynecol, Morsani Coll Med, Tampa, FL USA
关键词
Endometriosis; Endometrium; Angiogenesis; Primates; FACTOR CYTOPLASMIC DOMAIN; TISSUE FACTOR; STEM-CELLS; PRECLINICAL RESEARCH; ENDOTHELIAL-CELLS; GROWTH-FACTOR; BABOON MODEL; TUMOR-CELLS; PERITONEAL; EXPRESSION;
D O I
10.1016/j.repbio.2018.01.009
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:109 / 114
页数:6
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