Grants and Contracts Details

Description

Ovarian cancer is the most deadly gynecologic malignancy. Approximately 80% of women are diagnosed with advanced staged disease with a 5-year survival of only 40%. Clearly, innovative and effective treatment options are needed. One of the reasons ovarian cancer is so lethal is because M2, or immunosuppressive macrophages, accumulate in and around the tumor, which promotes cancer growth and spread. Since macrophages are able to change back and forth between the M2 and M1, or pro-inflammatory type, converting tumor macrophages to the M1 type is an attractive method for treating ovarian cancer. To do this, we have already developed Macrophage Derived Engineered Vesicles (MEVs) from human macrophages. In our preliminary, in vitro data, we show (1) tM1 MEVs are able to convert M2 macrophages into the M1 type, resulting in death of the ovarian cancer cells, (2) M1 MEVs specifically target tumors in mouse models, and (3) that MEVs have anticancer activity in ovarian cancer bearing mice. This suggests MEVs may be an effective and non-toxic treatment for ovarian cancer. The next step in developing MEVs as an anticancer agent is to determine a starting dose and to establish a manufacturing process. Taken together, the overall objective of this proposal is to establish the in vivo activity of the first therapeutic strategy designed to re-train an individual’s own immune system to eradicate ovarian cancer and set the stage for therapeutic human trials. Our team, with expertise in immunotherapy clinical trial design (Arnold), preclinical drug development (Kolesar), membrane biophysics (Richards), surgical oncology (Ueland) immunology (Bondada), and cell based manufacturing (Gedaly) has a strong track-record of productive collaboration and is well qualified to carry out the proposed work.
StatusActive
Effective start/end date7/1/226/30/24

Funding

  • KY Economic Development Cab

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.