Translating sarcoma antigen-directed co-stimulatory NK cells to the clinic
Despite attempts to improve treatment over the last few decades, children with advanced sarcomas of the muscle or bone continue to die from their disease. New treatments are sorely needed. Therapies that utilize the immune system to fight cancer, such as white blood cells that are engineered to target specific proteins on tumors, have shown promise in the lab. Their ability to cure patients, however, has been limited by a powerful tumor environment that inhibits the immune system. In addition, because there are very few ideal tumor target proteins (i.e., those expressed on the tumor, but not on normal tissues), it is difficult to spare normal cells from damage during therapy. Thus, there is an unmet need to develop therapies that safely target both the tumor environment and sarcoma-associated proteins, so that targeted immune cells can destroy cancer but leave normal tissue alone. To address this challenge, we have developed a cancer therapy using natural killer (NK) cells, a type of white blood cell with excellent tumor killing capacity and a unique ability to distinguish normal tissues. We have modified NK cells to express specialized proteins that will target both sarcoma cells and the tumor environment. With this approach, these NK cells would function only in the presence of both targets at sites of tumor while preventing damage to normal tissues.
Project Goal:
We have confirmed the ability of the NK cells to kill tumors safely in pre-clinical models and are now making plans to translate this therapy into a clinical trial for children with sarcomas. This involves producing the FDA-compliant genetic engineering tools to manufacture our specialized NK cells, the necessary regulatory testing, and regulatory approvals from our institution and the FDA. Overall, this project will help to launch a new type of immunotherapy into clinical trials for children with difficult-to-treat sarcomas.
