The Need

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 CAR expressing immune cells such as T and NK cells have shown promising results. 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 TF has been reported on cancer cells in a large number of cancers, including hematological cancers, as well as solid tumor cancers, including breast, lung, and skin cancers. There is a significant need to generate CAR-T and NK therapies targeting cancer specific TF expression, which holds a broad potential to treat patients with a variety of these malignant and non-malignant diseases.

The Technology

Innovative research in the laboratory of Dr. Zhiwei Hu at The Ohio State University College of Medicine and Comprehensive Cancer Center has led to new advances in the treatment of breast cancer. Dr. Hu’s technology utilizes CAR constructs that alter the patient’s own immune cells, including but not limited to T and NK cells, to effectively fight cancer. Dr Hu’s lab made CAR-expressing T and NK cells that target antigens expressed on cancer cells. The first target of this new technology is triple-negative breast cancer (TNBC), often considered an incurable malignancy once it spreads to the body due to a lack of effective therapy. Dr. Hu’s lab discovered that TF is a new target for TNBC and is commonly yet specifically expressed by the cancer cells (representing the majority of a tumor mass), tumor vascular endothelial cells (the inner layer of tumor neovasculature; supplying oxygen and nutrients for tumor growth and serving as conduit for metastasis), and cancer stem cells (contributing to drug resistance, metastasis and recurrence). Studies have demonstrated 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. The technology may be used in combination therapy with current standard of care or as a monotherapy. The technology also shows promise in treating non-malignant diseases involving pathological neovasculature, notably AMD, endometriosis, and rheumatoid arthritis.

CAR-T and CAR-NK are both being evaluated in a wide range of oncology settings. However, CAR-NK may overcome some of the limitations of CAR-T. First, clinical trials revealed that CAR-NK cell therapy are effective yet generally safer than CAR-T cell therapy. The administration of CAR-NK cells is not or less associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, which are often observed in many CAR-T clinical trials. The infused CAR-NK cells can persist for one year. Second, unlike CAR-T cells, CAR-NK cells retain an intrinsic capacity to recognize and target tumor cells through their native receptors. Lastly, NK cells do not require strict HLA matching and have less potential to cause graft-versus-host disease, making CAR-NK therapy compatible with both allogeneic and autologous treatment modalities.

Commercial Applications

• Targeted cancer therapy
• Adoptive CAR-T and CAR-NK cell therapy
• Cancer recurrence prevention
• Precision treatment for AMD, endometriosis, and rheumatoid arthritis

Benefits/Advantages

• Targets cancer cells, cancer stem cells, and pathological neovasculature
• Targets a wide range of diseases that express the tissue factor (TF) antigen
• May overcome drug resistance
• Prevents future cancer recurrence
• May be used in combination therapies or as a monotherapy

Research Interests

Dr. Hu is a world-class expert on tissue factor-targeted immuno-, gene, and photodynamic therapies, with more than 28 years of experience in solid cancer research. He has 46 granted or pending patents/ applications. His inventions have been the basis of two pharmaceutical startup companies and two clinical trials (in cancer and AMD).