Ovarian cancer is often diagnosed after tumor cells have already spread (metastasized) from the ovary, so it is difficult to remove them entirely using surgery and chemotherapy. Fortunately, there are cells naturally occurring in our immune system that have the ability to selectively destroy ovarian tumors without damaging healthy tissue, but they require stimulation to do so. For example, vaccines can train the immune system to fight ovarian cancer, and some of these are currently in clinical trials. However, vaccine therapies typically fail to expand anti-tumor immune cells enough to control metastatic diseases. They can also require months to mount an immune response, by which time the disease may become lethal.
We propose to create an injectable reagent that can quickly reprogram the patient’s immune cells (particularly T lymphocytes) to recognize and destroy ovarian tumors. Specifically, we hypothesize that T cells circulating in the blood can be genetically reconfigured by targeted, gene-bearing nanoparticles to express receptors that bind specifically to ovarian tumor proteins, which will enable them to bring about rapid and vigorous tumor rejection. Our preliminary experiments have already shown that a new type of nanoparticle we developed can efficiently transfer ovarian tumor-reactive receptor genes into T cells grown in the laboratory. We must now demonstrate that nanoparticle-mediated gene transfer can occur in circulating T cells. Our long-term goal is to integrate this approach into the standard-of-care for treatment of ovarian cancer.
The results of this project could substantially modify the way ovarian cancer patients are treated: a) Off-the-shelf nanoparticles that rapidly program existing T lymphocytes to recognize ovarian tumors could enable clinicians to treat diagnosed ovarian cancer patients immediately, before progression of the disease becomes irreversible. b) In contrast to standard chemoradiation therapies, nanoparticle-mediated targeting can direct T cells to selectively destroy only ovarian cancer cells, without damaging healthy tissue or producing toxic side effects. c) Just in the United States, more than 22,000 new ovarian cancer patients are diagnosed each year, so it is important that the DNA nanocarriers we are developing are amenable to fabrication on a large scale, and in a stable form. This means any ovarian cancer patient could be treated with T cell immunotherapy in an outpatient setting, and at reduced costs.