Collaborative science fuels innovation in immunotherapy effort to treat brain tumors

History is full of stories of individual scientists, such as Albert Einstein, whose discoveries made entire fields leap forward. However, science has progressed so much over the last century that no single researcher can keep up with all the information produced within a discipline. Instead, scientists now collaborate, bringing together complementary expertise to drive the next major discoveries.

St. Jude scientists Giedre Krenciute, PhD, Department of Bone Marrow Transplantation & Cellular Therapy, and Stephen Gottschalk, MD, Department of Bone Marrow Transplantation & Cellular Therapy chair and Center of Excellence for Pediatric Immuno-Oncology (CEPIO) co-director, are working to create better treatments for pediatric brain cancers. Collaboration is a key part of their approach, so much so that the pair received the Society for Immunotherapy of Cancer (SITC) Collaboration Award alongside their collaborators Sheila Singh, MD, PhD, McMaster University; and Sabine Heitzeneder, MD, and Crystal Mackall, MD, FAIO, Stanford University.

“It’s a nice recognition of our collaborative science from the premier society solely focused on immunotherapy in the United States,” Gottschalk said. “It’s a real validation that our peers in the field believe we are on the right path in our approach to creating better treatments for these diseases.”

“It means a lot to be recognized for our science,” Krenciute said. “The award really highlights how St. Jude researchers are working with other institutions to accelerate scientific discovery for pediatric cancers and translate those findings as quickly as possible into the clinic.”

Collaboration takes on two pediatric brain cancers

Adapting cellular immunotherapies, such as chimeric antigen receptor (CAR) T cells, to solid and brain tumors has been challenging. While successful in some hematological malignancies, CAR T cells have yet to deliver on their promise in most other tumor types, including brain tumors such as medulloblastoma and ependymoma. If standard therapy doesn’t work or these cancers relapse, patients have few therapeutic options and a poor prognosis.

To address the need for better treatments, the scientists sought to combine their efforts through collaboration to create T-cell-based immunotherapies with the potential to become standards of care for these diseases. “We cannot do it all by ourselves,” Krenciute explained. “We don’t have all the expertise needed here, nor do they have it at their institutions. By combining our complementary capabilities, we can move the science of immunotherapy for pediatric brain cancer further, faster.”

From St. Jude, Krenciute primarily studies cellular therapy for pediatric brain cancers, with a special emphasis on the tumor microenvironment. Gottschalk’s experience lies in cellular engineering and setting preclinical work up in a way that will most effectively translate into clinical testing. They also work with Stephen Mack, PhD, Department of Developmental Neurobiology, who is an expert in ependymoma, including modeling the disease, and Hongbo Chi, PhD, Department of Immunology chair and CEPIO co-director, who is an expert in T-cell immunology. The Stanford and McMaster groups bring expertise in medulloblastoma models and new immunotherapy target discovery.

“Even though these are two different types of brain tumors, what works in one model could be explored in the other,” Gottschalk explained. “And if it works in one and not in the other, we might be able to understand why, and that can also lead to additional advances.”

Research investment drives progress

To facilitate their collaboration, the scientists have shared monthly meetings during which each lab updates the others on their progress. This environment helps the researchers push to improve their science and share ideas, hopefully accelerating discovery. In addition, it allows trainees and early-career scientists to learn from those at other institutions. It also gives them the practical benefits of sharing expertise and materials to save time.

“We often share resources,” Krenciute said. “We regularly share cell lines and reagents, but also complementary skillsets. In one case, our collaborators needed high-resolution imaging of targets of interest; so, a trained microscopist in my lab performed the imaging to save them the time-consuming and expensive process of acquiring the right skills and hardware.”

As each group contributes its specialized knowledge, the scientists have chosen to take an egalitarian approach. “We’ve really created a co-equal multi-investigator collaboration between all three institutions,” Gottschalk said. “I think this award is a recognition that there’s really no comparable multicenter research collaboration focused on cellular therapy for pediatric brain cancer.”

“We have put a lot of resources into pursuing cellular therapies,” Gottschalk added. “This is national recognition that the investment is starting to pay off, and others see us as leaders in the field. Hopefully, we can use that recognition to collaborate with even more groups and find new standards of care for these ependymoma and medulloblastoma as quickly as possible.”