A novel, third generation tissue factor-targeting immunoconjugate (L-ICON3) and its uses
T2017-138 Tissue factor targeting agent aimed at fighting pathologic angiogenesis.
Tissue Factor (TF) is a cell surface receptor that is not expressed on normal vascular endothelial cells, the inner layer of normal blood vessel, and mediates coagulation in physiological condition. Under pathological conditions, TF is aberrantly expressed on the angiogenic vascular endothelial cells and also plays an important role in angiogenesis (the generation of new blood vessels). Pathologic angiogenesis is a key step in the many disease processes including that of disorders such as cancer (solid tumors and acute leukemia), age-related macular degeneration (AMD), endometriosis, and rheumatoid arthritis (RA). In cancer, TF is also overexpressed by the cancer cells and cancer stem cells in the tumor microenvironment. Therefore, agents that can bind TF in angiogenic endothelial cells, cancer cells and cancer stem cells could potentially be used to fight against a bevy of debilitating disease etiologies.
Researchers at The Ohio State University led by Dr. Zhiwei Hu developed L-ICON3, the third iteration of a powerful TF-targeting agent aimed at binding TF in angiogenic endothelial cells, cancer cells and cancer stem cells. L-ICON3 has demonstrated similar binding activities to cancer cells, and can generate stronger cytotoxicity to these cancer cells in vitro when compared to the original, clinical stage ICON and the second-generation (L-ICON1). L-ICON3’s molecular and genetic structures have been described. L-ICON3 has demonstrated a superior ability to initiate ADCC (antibody-dependent cell-mediated cytotoxicity) killing of target cells and a comparable ability to initiate complement-dependent cytotoxicity (CDC) in vitro. L-ICON3 has also exhibited stronger effects than the second-generation version in vivo for the treatment of triple-negative breast cancer, a currently incurable malignancy, in mouse models of human cancer line-derived and patient’s tumor-derived xenografts
- Treatment of Cancer and noncancerous diseases (AMD, endometriosis, RA)
- Targeted Cancer Immunotherapy
- Neovascular-targeted Immunotherapy
- Multiple applications for large number of potential patients
- Broad application for both benign and malignant disease
- Third generation; first two generations have strong supporting evidence and established research methods offering expedited future clinical testing for L-ICON3
- L-ICON3 demonstrates equivalent binding affinity and enhanced ability to induce ADCC and CDC killing in cancer cells when compared to previous ICON and L-ICON1, respectively
The Ohio State University laboratory that developed this technology has expertise in development of novel neovascular-targeted immunotherapy, gene therapy and photodynamic therapy for the treatment of pathological angiogenesis-dependent human diseases, notably cancer, AMD, and endometriosis. The researchers are interested in collaboration for further investigational and translational routes.