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

Demetra Hufnagel, Hufnagel D, Teddy G Goetz, Zhiwei Hu, Atunga Nyachieo, D'Hooghe T, Thomas D’Hooghe, Thomas D'Hooghe, Fazleabas A, Asgerally Fazleabas, Asgerally T. Fazleabas, Antoni J. Dulęba, Antoni Duleba, Duleba A, Graciela Krikun, Krikun G, Hugh S Taylor, Lockwood CJ, Charles J Lockwood
Reproductive biology · 2018 · vol. 18(1) , pp. 109–114 · doi:10.1016/j.repbio.2018.01.009 · PMID:29422377 · W2793886622
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An antibody-drug conjugate targeting the decorated oncofetal antigen resulted in regression of endometriosis lesions in baboons.

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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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Condition tags

endometriosis

MeSH descriptors

Adnexal Diseases Endometriosis Factor VII Immunoconjugates Immunoglobulin Fc Fragments Neovascularization, Pathologic Recombinant Fusion Proteins Thromboplastin Adenoviridae Adnexal Diseases Adnexal Diseases Adnexal Diseases Adnexal Diseases Amino Acid Substitution Animals Endometriosis Endometriosis Endometriosis Endometriosis Factor VII

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