Researchers at VCU Massey Comprehensive Cancer Center and the VCU Institute of Molecular Medicine (VIMM) have secured a $1.8 million US Department of Defense (DoD) grant to advance a novel cell therapy for advanced prostate cancer.
The team will use the three-year DoD award to study a new approach using engineered natural killer (NK) immune cells. These cells are designed to deliver a potent, engineered protein called IL-24 “Superkine” (IL-24S) directly to prostate cancer tumors.
The research is led by Dr. Paul B. Fisher and Dr. Swadesh K. Das. IL-24S is a modified version of a natural immune signaling protein that has shown an ability to selectively kill cancer cells while sparing healthy ones. Previous work delivered IL-24S via a therapeutic virus to treat brain cancer (glioblastoma). This new project employs enhanced NK cells as the delivery vehicle.
The Challenge of Castration-Resistant Prostate Cancer
While early-stage prostate cancer is often curable, advanced disease that becomes resistant to hormone therapy—castration-resistant prostate cancer (CRPC)—and spreads to bone lacks effective treatments. An underlying problem with prostate cancer diagnosis and treatment is the absence of a definitive test that will inform a physician if a patient’s PC will remain slow-growing and responsive to therapy, or if it will evolve into an aggressive form, leading to CRPC, with the capacity to metastasize and with no effective therapy,” Fisher said.
The new strategy involves genetically modifying NK cells with chimeric antigen receptors (CAR) that target prostate-specific membrane antigen, a common marker on prostate cancer cells. These CAR-NK cells will then be further engineered to produce the IL-24S protein locally at the tumor site.
The foundation for this work was bolstered by a study published in the Journal for ImmunoTherapy of Cancer in June. That research demonstrated that IL-24S could be fused with another immune modulator, IL-15, creating a “Fusion Superkine.” In preclinical models of brain cancer, this fusion protein enhanced the anti-tumor activity of immune cells. The data indicated the approach could potently activate immune responses, supporting its investigation in other cancers like prostate cancer.
Research Aims and Potential Impact
The DoD grant will fund two primary aims: defining the mechanisms by which IL-24S activates and sustains NK cells in the body, and determining how it boosts those cells’ ability to fight CRPC.
Preliminary animal studies are promising. “Initial animal PC modeling studies indicate that autologously delivering IL-24S ‘Superkine’-modified NK cells can effectively treat primary and advanced prostate cancer,” Fisher noted.
If successful, this combined CAR-NK and Superkine approach could control or eliminate CRPC and its bone metastases. Fisher remarked that these applications could offer an optimal solution and potentially enhance patients’ quality of life in the long run.
