Cancer continues to be a leading cause of death in the U.S. and in many other countries. Cancers develop and spread within the body when tumor cells are not detected or destroyed by the immune system. Although certain new therapies hold promise, current cancer treatments, including chemotherapy and radiation therapy, tend to kill cells non-selectively and can cause harm to the patient. It is, therefore, critical to develop immunotherapeutic approaches that will enable the patient's immune system to recognize the cancer cells and eliminate them. The advantage of immunotherapy over the existing treatment approaches is that immune response to tumors is specific, safe, and has a memory component that can safeguard the body against newly arising tumors. T-cell response directed at tumor antigens is critical to the prevention and elimination of cancer cells. T cells require three distinct signals for activation; Signal 1 is antigen specific and mediated by the T-cell receptor interaction with the antigen, Signal 2 is mediated by receptor and ligand interactions, such as CD40/CD40L and CD28/B7, and Signal 3 is mediated by cytokines. Lack of signal 2 or co-stimulation is a critical mechanism used by many tumors for the evasion of the immune system. In this application, we propose to use a proprietary technology called ProtExTM to place a novel costimulatory protein, SA-hCD40L, on the surface of ovarian tumor cells in less than 2 hours. When present on the tumor cell surface, the protein is expected to activate key cells of the patient's immune system to mount an anti-tumor response. This may result in physical elimination of tumor cells, even at distant sites in the body. During this project we will display SA-hCD40L on the surface of human tumor cells of ovarian origin and test whether these cells can generate anti-tumor immune responses in peripheral blood lymphocytes harvested from healthy individuals and ovarian cancer patients. In vitro proof-of-concept for this approach will allow us to test the efficacy of this approach for cancer immunotherapy in the clinic. In the longer term, we will develop and market an anti-tumor vaccine containing SA-hCD40L. Use of the vaccine will lower the death rate and improve the quality of life of cancer patients. The long-term success of this project will lead to more effective treatment of cancer in a way that preserves the patient's overall health ? ?
