From using artificial intelligence to address a treatment-resistant form of leukemia to combining ultrasound technology and potent T cells to treat brain tumors in pediatric patients, this year's NEMO Prize-winning USC researchers exemplify the award's founding mission.
Launched in 2023 through a gift from Shelly and Ofer Nemirovsky, the annual NEMO Prize competition supports collaborations between researchers at the USC Viterbi School of Engineering and the university's constellation of health sciences schools.
"In a moment where university budgets are tighter than ever, funding from private sources for smart ideas in their nascent stages is critical," said Shelly Nemirovsky, a USC trustee and 1985 graduate of the university. "So often those dollars come when the path to success is evident, but who can say how many potential cures for devastating diseases have been lost or delayed because scientists couldn't afford to test their theories?"
The NEMO Prize is a highly selective award, focused on projects that do not qualify for support by federal agencies and are not yet mature enough for private investment.
"The therapies initiated through these awards have the potential to cure two terrible diseases with notoriously low survival rates," said Steven D. Shapiro, senior vice president for health affairs. "Through innovative uses of medical technology, these scientists are creating the next generation of therapies that so many cancer patients are counting on for a cure."
AI-fueled innovation
Acute myeloid leukemia (AML) is a difficult-to-treat disease that progresses rapidly with a high chance of recurrence. For NEMO Prize winners Keyue Shen, an associate professor of biomedical engineering at USC Viterbi, and Yali Dou, a professor in the department of medicine and cancer biology at the Keck School of Medicine of USC, the disease's resistance to treatment offers opportunities for new approaches to identifying biomarkers that can predict how well certain therapies work for patients.
The duo says that leukemia cells have unique metabolic profiles and can dynamically change when cells are under stress during treatment. They can also rewire the way they use nutrients to support their fast growth. As a result, the metabolic profiles provide a wealth of information about the leukemia cells. With the support of the NEMO Prize, Shen and Dou hope to turn the metabolic signal into a predictive biomarker for AML, which could help clinicians tailor therapies earlier and more precisely.
Dou said that AML is a disease that affects older patients very aggressively. Patients often don't have very good drug response and cannot tolerate intensive chemotherapy.
"That's why precision therapy is needed to treat AML patients," Dou said. "When I talked to Keyue, he had this very cool technology that captures the metabolic features in live cells and then uses them to develop drug-response-prediction through AI."
While imaging has been used in the past as a tool to predict cancer treatment, Shen and Dou say that they will be the first group to perform an AI-based analysis of metabolic signature extraction from single cell images and use that information to predict therapeutic responses in AML patients.
"As the therapy moves into the precision medicine arena, I think this type of new technology could really make a difference," Dou said.
The team is also collaborating with the USC Norris Comprehensive Cancer Center, where Dou serves as the associate director for basic science and co-leads the leukemia biorepository with Eric Tam.
"I think access to primary samples will help facilitate quick translation of this technology onto human patients," Shen said.
Combining methodologies for impact
The goal of tackling high-grade glioma (HGG) brain tumors - a leading cause of cancer-related deaths in children with a five-year survival rate of only 20% - brought together researchers Yingxiao Wang, professor and chair of the department of biomedical engineering at USC Viterbi; USC Viterbi Assistant Professor Longwei Liu; and Keck School of Medicine Assistant Professor of Pediatrics Sarah Richman, who serves as a transplant and cell therapy physician at Children's Hospital Los Angeles.
The team's NEMO Prize-winning proposal merges leading-edge molecular engineering (Wang and Liu) with pediatric brain tumor-targeted chimeric antigen receptor (CAR) T cell research (Richman) with the goal of improving quality of life and curing cancer in young patients.
The success of CAR T cell immunotherapy in treating certain kinds of leukemia has generated huge interest in applying that therapy to pediatric HGG patients, whose tumors are particularly lethal and resistant to treatment. The team said that lackluster responses to current efforts have highlighted the need for more potent CAR T cells to address the disease. Unfortunately, one major risk in using these cells is unacceptable levels of toxicity in nearby, non-tumor tissue.
Richman's lab has focused on trying to understand how to make CAR T cells more effective and safer for patients who have brain tumors and solid tumors. Even before all three members of the team got to USC (Richman in 2020 and Wang and Liu in 2023), the trio met over Zoom to discuss how to apply ultrasound-controllable technology to Richman's work.
"Our method is using ultrasound to control those CAR T, which will allow us to really bump up treatment efficacy, while at the same time allowing us to maintain safety," Wang said. "Ultrasound-controlled CAR T can contain the therapy to the local tumor region and wouldn't cause toxicity outside the tumor."
The ultrasound-controlled strong CAR is used in combination with a weaker, standard CAR to safely target any microscopic cancerous cells in surrounding brain tissue.
"Both sides were super excited about the research happening at the different labs," Liu said.
Richman agreed. "This approach has the potential to raise the ceiling of how strong CARs can be because we have Peter's and Longwei's brilliant platform for controlling where the CAR T cells can be turned on," she said. "The potential result is more effective CAR T cells for brain tumor patients."
The team hopes that within the next five years they can treat their first brain tumor patient with the project's ultrasound-controlled CAR plus standard CAR combination product. The success of this combination therapy could expand the project's scope beyond its initial target population, creating treatment opportunities for other cancers and diseases.
The team believes their ability to combine their complementary fields of expertise around a common goal has been instrumental to their success so far.
"The NEMO Prize will be critical for us to test the idea we want to implement to demonstrate feasibility and obtain more support from other funding agencies to move the project towards eventual clinical trials," Wang said.
Imagination ignited
As both teams look ahead to taking their research proposals to the next level, they appreciate the infrastructure for collaboration that the university provides, as well as the vote of confidence and financial support from the prizes.
"The establishment of the NEMO Prize itself is a testimony that USC and the prize leaders are really trying to bring the engineering and technology world together for medical applications," Liu said. "The beauty of USC specifically is its researchers and faculty who are open-minded and willing to reach out to work together."
For the Nemirovskys, the enduring appeal of the prizes is the latent potential in each year's award-winning partnerships.
"The NEMO Prize focuses on collaboration between engineering and medicine because it's in that intersection where anything is possible," Shelly Nemirovsky said. "In isolation, those disciplines may not recognize their potential, but in combination, imagination is ignited."
