The immunoconjugate "icon" targets aberrantly expressed endothelial tissue factor causing regression of endometriosis.
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.
Krikun
Graciela
G
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University, School of Medicine, New Haven, CT 06520-8063, USA. graciela.krikun@yale.edu
Hu
Zhiwei
Z
Osteen
Kevin
K
Bruner-Tran
Kaylon L
KL
Schatz
Frederick
F
Taylor
Hugh S
HS
Toti
Paolo
P
Arcuri
Felice
F
Konigsberg
William
W
Garen
Alan
A
Booth
Carmen J
CJ
Lockwood
Charles J
CJ
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
D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D013925:Thromboplastin