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Development of a Novel Vaccine With Fusions of Dendritic and Ovarian Cancer Cells from Patients

Principal Investigator: GONG, JIANLIN
Institution Receiving Award: BOSTON UNIVERSITY, BOSTON CAMPUS
Program: OCRP
Proposal Number: OC990033
Award Number: DAMD17-00-1-0572
Funding Mechanism: Idea Award
Partnering Awards:
Award Amount: $514,500.00


PUBLIC ABSTRACT

Ovarian cancer is one of the most common malignancies affecting women in the United States. It is estimated that 25,000 new cases are diagnosed each year. Approximately 70% of women present with advanced stage disease since there are no effective screening methods and few symptoms in the early stage. Therefore, about 14,000 women will die from the disease. Surgery, radiation, and chemotherapy are the standard treatments, which have side effects and are often ineffective for advanced ovarian cancer. Development of an effective vaccine for the treatment of ovarian cancer can significantly improve women┬┐s health.

We propose a novel approach using fusion of patient-derived dendritic cells (DC) with autologous ovarian cancer cells as a vaccine for the treatment of advanced ovarian cancer. The MUC1 and CA-125 antigens are tumor-associated antigens that are overexpressed in human ovarian cancer and can serve as targets for immunotherapy. DC are potent immune cells that excel in antigen presentation and the initiation of T cell-mediated immunity. The fusion cells can be constructed in such a way that they are equipped with DC-derived costimulatory molecules, which are essential for the induction of antitumor immunity, and tumor antigens, which serve as a guiding system to target tumor cells.

In previous studies, mice vaccinated with fusion cells did not develop tumors when injected with cancer cells. Most significantly, MUC1 transgenic mice with established MUC1-positive tumor cells in the lungs were cured of disease after receiving the vaccine. The proposed work will extend these findings to human situations and develop a fusion cell vaccine from patient-derived DC with ovarian cancer cells. The fusion cells will be characterized and their functions will be determined. This study will lead to a human fusion cell vaccine ready for clinical trial.