Duke Scientists Receive NCI R01 Grant
The National Cancer Institute (NCI) awarded $2.1 Million to Duke Cancer Institute (DCI) researchers to study plasmonic nanoparticle-mediated immunotherapy to treat metastatic bladder cancer.
Co-principal investigators, Brant Inman, MD, MS, and Tuan Vo-Dinh, PhD, developed a novel two-pronged treatment approach utilizing nanotherapy and immunotherapy, a treatment they refer to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY), to enhance the efficacy of immunotherapy for bladder cancer.
“Duke University prioritizes collaborations between medicine and engineering, by providing seed grants for developing ideas,” explained Inman, co-chair of the DCI Center for Prostate & Urologic Cancers. “Surgeons at Duke have a long tradition of innovating alongside engineering colleagues, and both Duke School of Medicine and Duke Biomedical Engineering Department are top 10 programs in the United States. Together, there is a lot of brainpower to solve difficult medical and surgical problems, and I believe the partnership between engineering and medicine is one of the most defining aspects of Duke’s research portfolio.”
Hyperthermia (HT) is a therapeutic modality that has the ability to boost immune responses, improve drug delivery and improve cancer cell sensitivity to the therapy. In the past decade, nanomaterials have emerged as an important method of achieving local HT. Plasmonic nanoparticles have unique properties that allow them to amplify laser light, thus increase the effectiveness of light-based photothermal tumor ablation.
The SYMPHONY concept combines plasmonic gold nanostar (GNS) mediated photothermal therapy with anti PD-L1 immunotherapy for a two-pronged treatment approach for bladder cancer. GNS in synergy with a laser is able to efficiently generate heat resulting in ablation of the tumor. Following ablation, dying tumor cells release tumor-specific antigens and heat shock proteins. Antigen-presenting cells process the tumor antigens and present tumor-derived peptides to T cells, triggering the immune response. Anti-PD-L1 therapy blocks mechanisms that tumors use to protect themselves from being attacked by immune cells.
“The R01 grant is the second awarded grant that my lab shares with Dr. Vo-Dinh,” said Inman. “Through this award, we will be able to understand and further exploit the mechanism underlying these novel synergistic therapies. As we continue our work on SYMPHONY, we expect new ideas to sprout and impact our research results.”
Preliminary results have shown that SYMPHONY not only eradicates primary ‘treated’ tumors but also resulted in the immune-mediated destruction of distant ‘untreated’ metastatic tumors, working like both a primary ablative treatment and a vaccine simultaneously. Currently, the research is being tested in bladder cancer, but researchers hope to test this concept in brain, breast and lung cancer.