Icon immunoconjugate treatment results in regression of red lesions in a non-human primate (Papio anubis) model of endometriosis |
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| Authors: | Demetra Hufnagel Laura G Goetz Zhiwei Hu Atunga Nyachieo Thomas D’Hooghe Asgerally Fazleabas Antoni Duleba Graciela Krikun Hugh S Taylor Charles J Lockwood |
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| Institution: | 1. Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, United States;2. Department of Surgery, The Ohio State University College of Medicine, Columbus, OH, United States;3. Department of Reproductive Health and Non-Communicable Diseases, Institute of Primate Research, Nairobi, Kenya;4. Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven (University of Leuven), Campus Gasthuisberg, Leuven, Belgium;5. Department of Obstetrics, Gynecology, and Reproductive Biology, Michigan State University, Grand Rapids, MI, United States;6. Department of Reproductive Medicine, University of California San Diego, San Diego, CA, United States;7. Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, United States |
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| Abstract: | 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. |
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| Keywords: | Endometriosis Endometrium Angiogenesis Primates |
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