L-ICON3 Suppresses Endometriosis in a Murine Model.

Endometriosis is a chronic, systemic gynecological disorder that affects 190 million women worldwide. Current treatments consist of hormonal suppression and surgical excision; however, both have considerable side effects and a high risk of recurrence. Here, we report a systemic therapy to treat endometriosis by L-ICON3, a novel chimeric immunoconjugate molecule that binds to tissue factor (TF), which is upregulated in endometriosis. Endometriosis was induced in mice by implanting endometrium from donors and that developed into experimental endometriosis after 6 weeks. Mice were then randomly assigned to three groups (n = 12 per group). Group 1 received recombinant L-ICON3 treatment, whereas group 2 and 3 received PBS and an IgG isotype control, respectively, for an additional 6 weeks. Then mice were euthanized, and endometriotic lesions were collected and analyzed. Primary outcomes included lesion size and endometriosis wall thickness, and immunohistochemistry staining for immune markers. L-ICON3-treated mice demonstrated 2.5-fold decrease in lesion size and endometriosis wall thickness, as well as enhanced recruitment of T and NK cells into lesions, while also showing a significant decrease in TF expression compared to treatments with isotype control IgG or PBS. Our findings demonstrate the L-ICON3 is a promising novel therapeutic approach for the treatment of endometriosis that selectively binds TF and recruits T and NK immune cells into the lesions.