EON: Eradicating Ovarian Cancer Now with Personalized Nanoparticles

Health Problem. Ovarian cancer is a highly deadly disease. The American Cancer Society estimates 19,680 new diagnoses and 12,740 deaths will occur in 2024.1 There are no methods for identifying ovarian cancer early and women who develop ovarian cancer are treated for 6 months with traditional chemotherapy, which has been the standard treatment for almost 30 years. While most women initially benefit from this treatment, more than two out of three will have their cancer recur.2 Current Approach and Limitations. After completing initial therapy, there are only two FDA approved treatments that women can take to prevent a recurrence. The first is a drug called bevacizumab which does not improve survival compared to doing nothing and causes serious adverse effects like bleeding and blood clots.3 The second is niraparib which works for about one in ten women but also causes severe diarrhea and nausea.4 Like most cancer treatments, bevacizumab and niraparib are not cancer-specific and activity is limited by off target toxicity. A newer approach is based on the idea that the high rate of ovarian cancer recurrence is caused by small numbers of cancer cells remaining after initial treatment. These cells live in a pro-cancer environment, which supports their growth and spread.5 Immune therapies, including immune check point inhibitors, CAR-T cells, TILs, and monocytes, that activate the patient’s own immune system have been tried to eradicate these persistent cancer cells, however they have been ineffective, toxic or both.5-8 Novelty. The serious and sometimes fatal toxicity associated with immune therapy is caused by eliciting an intense and non-specific immune reaction. Our first game changing advance is overcoming toxicity by pivoting away from whole cell-based immune therapies and to extracellular vesicles. Extracellular vesicles are ~150nm particles released by most cells that function in cell-to-cell communication.9 Key advantages of vesicles are cell specificity which triggers local immune responses. Vesicles are under investigation for a number of indications and have reached clinical trials for infectious disease,10 but significant barriers to commercialization are present.11 Vesicles are typically manufactured by culturing cells, stimulating them to release vesicles and then isolating the vesicles, which very low yields (1 million vesicles per mL of culture). A typical dose of vesicles is 1 billion, requiring a 1000 mL of culture per dose.11 Our second key advance is developing a broad platform technology to generate cell-derived vesicles from any cell. These cell derived vesicles retain the desirable functional and targeting properties of endogenous vesicles while overcoming insurmountable limitations in yield. Our yields of vesicles are ~1800 vesicles per cell or 100 billion per mL of apheresis product; a 100,000 fold improvement over isolation of endogenous vesicles from culture. Our cell-derived vesicles also have desirable drug-like characteristics including a ~48hr half-life, stability at 4C for upto 3 months and ability to be lyophilized for long term storage. Figure 1: Overview of MEV Production and Mechanism