Methods for generation of TF-targeting chimeric antigen receptors (CARs)-natural killer cells and T cells
A therapeutic application of neovascular-targeting chimeric antigen receptor (CAR) T cells and NK cells for treating diseases associated with pathological angiogenesis, in which TF is abarrently expressed, such as solid tumors, leukemia, lymphoma, age-related macular degeneration (AMD), endometriosis, and rheumatoid arthritis.
Nearly 2,000,000 new cancer cases are expected to be diagnosed each year in the United States. Available treatment options include surgery, radiation therapy, chemotherapy, and immunotherapy. Recently, cell-based immunotherapy utilizing specific chimeric antigen receptor (CAR) expressing immune cells such as T and natural killer (NK) cells have shown promising efficacy. CAR therapy re-programs T and NK cells to recognize specific antigens on the surface of cancer cells and eliminate them. Different types of cancer cells can express different antigens. Specifically, the expression of tissue factor (TF) has been reported in a large number of cancers, including glioma, pancreatic cancer, non-small cell lung cancer, esophageal, gastric, colorectal cancer, ovarian cancer, breast cancer, prostate cancer, and hepatocellular cancer. There is therefore a need for the technology to generate CAR-T and NK cells against cancer specific TF.
Innovative research in the lab of Dr. Zhiwei Hu at The Ohio State University College of Medicine has led to a new advance in the treatment of breast cancer. Dr. Hu’s technology is a group of novel specifically targeted CAR constructs, that can alter the patient’s own immune cells, including T and natural killer cells, to effectively fight cancer. The method uses genetically modified T and NK cells that express CARs against the TF antigen expressed on cancer cells. The first target of this new technology is triple-negative breast cancer (TNBC), often considered an incurable malignancy due to a lack of targeted therapy. Studies are ongoing to investigate the efficacy and safety of the new technology in preclinical animal studies, with the goal to further develop and ultimately commercialize this new cancer fighting technology for patients with TNBC, as potentially a first line treatment alternative. Additional targets include other pathological neovasculature-involved in human diseases, notably other solid cancers, acute leukemia, macular-degeneration, endometriosis, and rheumatoid arthritis.
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.