Key Points
- Researchers are investigating multiple ways that focused ultrasound could improve pancreatic cancer treatment in laboratory studies.
- Projects include enhancing the delivery of chemotherapy and stimulating the immune system to fight this devastating disease.
Preclinically, researchers are investigating multiple ways that focused ultrasound could improve pancreatic cancer treatment. From enhancing chemotherapy delivery and stimulating the immune system to developing new treatment approaches and preclinical models, many laboratory studies will accelerate future clinical research. Six active projects are described below.
University of Oxford researchers Keaton Jones, BMBS, DPhil, FRCS, and Michael Gray, PhD, are investigating whether high intensity focused ultrasound can improve immunotherapeutic responses in pancreatic cancer in a mouse model. If focused ultrasound can boost the immune system and potentially increase the delivery and efficacy of immunotherapy drugs, the results of this study may lead to the identification of novel therapeutic combinations for pancreatic cancer. This project is being jointly funded with Pancreatic Cancer UK.
Histotripsy and thermal ablation have both been shown to induce a systemic anti-tumor immune response, but the mechanism behind this response remains unknown. Research led by Irving Coy Allen, PhD, MBA, in the Department of Biomedical Sciences and Pathobiology at the Fralin Biomedical Research Institute at Virginia Tech Carilion, involves studying tumor antigen presentation and quality after both types of ablation to evaluate the effectiveness of each modality. In their project titled “Defining the Abscopal Effect in Pancreatic Cancer Following Focal Tumor Ablation,” the team hopes to answer the question of which method induces the most robust and predictable abscopal effect.*
In a project titled, “Maximizing Systemic Anti-Tumor Immune Responses in Pancreatic Cancer Using Histotripsy in Combination with Immunotherapeutic Approaches,” Irving Coy Allen, PhD, MBA, in the Department of Biomedical Sciences and Pathobiology at the Fralin Biomedical Research Institute at Virginia Tech Carilion, is seeking to determine whether the application of histotripsy can change immunologically challenging, or “cold,” tumor microenvironments into immunotherapy-responsive, or “hot” environments. If successful, the team may be able to improve the effectiveness of immunotherapies for pancreatic cancer while also gaining further understanding of the abscopal effect (tumor regression in locations that were not directly treated with focused ultrasound). This project originated as a result of the Foundation’s workshop on The Role of Focused Ultrasound in Pancreatic Cancer.*
In “A Rational Comparison of Thunder, Fire, and Lightning for Igniting an Anticancer Immune Response in Solid Tumors,” Matthew DeWitt, PhD, and his team at the University of Virginia are comparing and combining three different types of focused energy—ultrasound heating, ultrasound mechanical destruction, and electricity—to kill cancer cells and boost immune therapies. This project is evaluating how ablation technologies affect immune response and testing combination approaches. If successful, such ablation techniques could be used to treat metastatic cancers like those of the breast and pancreas.*
Anutosh Ganguly, PhD, MBA, at the University of Michigan is investigating how histotripsy can improve cancer treatment outcomes. The project, “Enhancing Post-Histotripsy Anti-Tumor Immune Responses and Drug Delivery via Tumor Vascular Normalization in Pancreatic Adenocarcinoma,” focuses on addressing a key challenge in treating pancreatic cancer: abnormal blood tumor vessels that create a hostile microenvironment by reducing oxygen and blocking immune cell access and drug delivery. Because initial findings showed that histotripsy reduces tumor hypoxia, stimulates anti-tumor immune responses, and improves chemotherapy delivery, the current research aims to determine whether these benefits occur through vascular normalization (improving blood vessel structure and function), potentially creating a more practical approach to delivering chemotherapy in pancreatic cancer models.
Virginia Tech researchers Eli Vlaisavljevich, PhD, and Irving Coy Allen, PhD, developed a novel large-animal model for pancreatic cancer research, enabling more effective preclinical testing of treatments. The team used genetically modified immunocompromised pigs successfully engrafted with human pancreatic tumors, allowing them to test histotripsy. Initial results demonstrated histotripsy’s potential effectiveness while highlighting technical challenges with ultrasound guidance, establishing a viable treatment approach, and a valuable model for testing various biomedical devices.*
*This project was funded by the Commonwealth of Virginia as a result of the Foundation’s advocacy efforts.