Kevin Osteen
Last active: 2/19/2015

The immunoconjugate "icon" targets aberrantly expressed endothelial tissue factor causing regression of endometriosis.

Krikun G, Hu Z, Osteen K, Bruner-Tran KL, Schatz F, Taylor HS, Toti P, Arcuri F, Konigsberg W, Garen A, Booth CJ, Lockwood CJ
Am J Pathol. 2010 176 (2): 1050-6

PMID: 20042667 · PMCID: PMC2808107 · DOI:10.2353/ajpath.2010.090757

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.

MeSH Terms (20)

Adult Animals CHO Cells Cricetinae Cricetulus Drug Delivery Systems Endometriosis Endothelium, Vascular Female Humans Immunoconjugates Immunoglobulin Fc Fragments Immunotherapy Mice Mice, Nude Middle Aged Neovascularization, Pathologic Peritoneal Diseases Thromboplastin Transplantation, Heterologous

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