title: The immunoconjugate "icon" targets aberrantly expressed endothelial tissue factor causing regression of endometriosis.
abstract: 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.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University, School of Medicine, New Haven, CT 06520-8063, USA. graciela.krikun@yale.edu
authors.forename: Graciela
authors.initials: G
authors.lastname: Krikun
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Hu
authors.forename: Kevin
authors.initials: K
authors.lastname: Osteen
authors.forename: Kaylon L
authors.initials: KL
authors.lastname: Bruner-Tran
authors.forename: Frederick
authors.initials: F
authors.lastname: Schatz
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
authors.forename: Paolo
authors.initials: P
authors.lastname: Toti
authors.forename: Felice
authors.initials: F
authors.lastname: Arcuri
authors.forename: William
authors.initials: W
authors.lastname: Konigsberg
authors.forename: Alan
authors.initials: A
authors.lastname: Garen
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Booth
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lockwood
mesh_terms: D000328:Adult; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D016503:Drug Delivery Systems; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000494:pharmacology*; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000494:pharmacology; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000628:therapy*; D010532:Peritoneal Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D013925:Thromboplastin