Dual-Modality Ultrasound and Photoacoustic Molecular Imaging Strategies for Aggressive Prostate Cancer Detection

Prostate cancer is the fourth most common cancer globally and the second leading cause of cancer death among men in the United States. In the United States alone, there are approximately 2.8 million men living with prostate cancer. Prostate cancer is a disease of older men, with the average age of diagnosis being 66 years. As a substantial proportion of Veterans are men and the median age of Veterans is 64 years, this group has an elevated risk for prostate cancer. Prostate cancer is the most common malignancy in Veterans and is diagnosed in approximately 11,000 men in the VA system each year. Military Veterans exposed to Agent Orange during the Vietnam War have a particularly increased risk of prostate cancer. Prostate cancer cells show high-level expression of a protein called Prostate Stem Cell antigen (PSCA). 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 tumors 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 PSCA for the treatment of prostate cancers and to demonstrate their efficacy and safety using preclinical studies. At the end of the project period, we hope to have demonstrated the safety and efficacy of PSCA SIR T cells, which will lay the foundation for initiation of Investigational New Drug application-enabling studies. In the long term, the PSCA-SIR-T cells developed by this project could potentially revolutionize the treatment of prostate cancers, as a single injection of PSCA-SIR-T cells could potentially result in long-term remission and perhaps a cure of even advanced castrate-resistant metastatic disease. The PSCA-SIR-T cells of the current proposal could be also combined with other forms of immunotherapy, hormonal therapies, and/or targeted therapies to further improve the response rate or duration of remission. The project is highly relevant to military health, as prostate cancer is the most common malignancy among the military Veterans who are at high risk of prostate cancer due to their age and exposure to Agent Orange during the Vietnam War.