From powering up tired immune cells with a burst of oxygen to programming spongy scaffolds to repair bone and deliver therapy, the newest Pilot Projects are underway thanks to funds raised for the 2024 Prouty.
Programming cryogels to deliver bone cancer therapeutics
Osteosarcoma is the most common type of bone cancer in children. Current treatments such as surgery and chemotherapy can be tough on patients and leave a critical need to rebuild healthy bone after surgery.
Previous studies in tissue engineering have shown that cryogels, which are a spongy, durable scaffold, can promote bone formation by cellular trafficking. In a new Prouty Pilot research project, Dartmouth Cancer Center scientists Katherine Hixon, PhD, and Hung Nguyen, PhD, are experimenting with cryogels to see if the structures can be programmed using ultrasound waves to release growth factors that would help rebuild bone and also deliver cancer therapeutics directly to the disease site. Ultrasound-responsive cryogels could offer an alternative to bone grafts as a less invasive way to help pediatric patients repair bone while also targeting any remaining cancer cells, ultimately improving the prognosis of osteosarcoma.
A second wind for immune cells
Immunotherapy uses the body’s own natural defenses against cancer. However, immune cells, called T cells, can become exhausted when their job is too difficult and goes on too long. One factor that exhausts T cells is the low oxygen content in many tumors. In a new Prouty Pilot, cancer researchers Jay C. Buckey, Jr., MD, Edward J. Usherwood, PhD, and Judy Rees, BM, BCh, MPH, PhD, want to understand whether T cells can be strengthened by getting more oxygen into the tumor.
Hyperbaric oxygen therapy (HBOT) increases oxygen in the body tissues by delivering it to the patient’s lungs at high pressure. The team will look to see whether immune T cells in specially grown melanoma models will be healthier for longer if treated with HBOT, and which HBOT conditions have the best effect on oxygenation within the tumor. They’ll then use these optimal conditions to study the impact of HBOT on T-cell exhaustion and tumor growth, potentially leading to better outcomes for thousands of patients whose immunotherapy would not otherwise work effectively.
Trans-oral surgery goes 3D
Morbidity associated with trans-oral or throat cancer surgery has significantly reduced over the past 2 decades, thanks to newer less invasive laser and robotic surgery techniques. However, because the incidence of these cancers is increasing and the primary treatment is still a complicated surgery of an “inside-out” nature, further improvement is needed. The three-dimensional (3D) complexity of the throat and the surgeon’s inability to feel the margins, or edges of cancerous tissue, present significant challenges when it comes to accurately cutting along the underside of tumors.
Cancer researchers Joseph Paydarfar, MD, Ryan Halter, PhD, and Michael Kokko, PhD, are using Prouty dollars to develop new technologies to improve the safety and efficacy of trans-oral throat cancer surgery. In their new project, they will pair localization markers, similar in concept to those used for breast cancer surgery, with image guidance to improve margin control and to aid in the virtual 3D reconstruction and orientation of throat tumors.
New models for studying cancer
Xenograft models are made by transplanting tissues, organs, tumors and even single cells from one species to another. Such models are essential for proving the safety and feasibility required to advance promising pre-clinical concepts to humans. However, sometimes, the models lack the characteristics needed for studying new imaging and surgical techniques, such as fluorescence-guided surgery.
Principal Investigators Matthew LeBoeuf, MD, Eunice Chen, MD, PhD, and Kimberley Samkoe, PhD, are improving upon the xenograft concept by developing new genetically induced models of squamous cell (skin) carcinoma. Their goal is to build on their earlier success with lab models that demonstrated improved diagnostic accuracy and speed of tumor margin detection. Once in place, these new genetically induced models will open the door to advancing a number of imaging and surgical endeavors.
Save the Date! The next Prouty fundraiser to support life-saving cancer research and patient support services will take place on July 12, 2025.