Next-Generation Chimeric Antigen Receptor T Cells Targeting FOLR1 for the Treatment of Ovarian Cancer
Abstract
Ovarian cancer is the leading cause of cancer mortality in the United States. A majority of patients with ovarian cancer show high level expression of a protein called Folate Receptor ? (FR?). Chimeric antigen receptor T (CAR-T) is a novel approach to genetically engineer immune cells to kill cancer cells. Despite the success of CAR-T in blood cancers, there are several limitations to this approach including lack of efficacy against solid tumor and toxicities. To overcome the above design limitations of the current generation CARs, we have developed a next generation platform, designated Synthetic Immune Receptor (SIR). The main objective of the proposal is to generate a panel of SIRs targeting FR? for the treatment of ovarian cancers and to demonstrate their efficacy and safety using preclinical studies. Thus, the project’s area of emphasis is to develop novel therapeutic strategies for treatment and prevention of ovarian cancer. At the end of the project period, we hope to have demonstrated the safety and efficacy of FR? SIRs using pre-clinical studies and selected the optimal SIR construct which will lay the foundation for confirmatory studies before the initiation of human clinical trials in 5-6 years. In the long term, the FR? SIR developed by this project could potentially revolutionize the treatment of ovarian cancers as a single injection of FR? SIR could potentially result in long-term remission and perhaps cure of even advance metastatic disease. The FR? SIR of the current proposals could be also combined with other forms of immunotherapy and/or targeted therapies to further improve the response rate or duration of remission. The project is relevant for military health as, according to Military Health Service data, over 20,000 DOD beneficiaries were diagnosed with ovarian cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310506
Entities
People
- Preet Chaudhary
Organizations
- United States Army
- University of Southern California