Engineered virus therapy triggers powerful immune responses in glioblastoma

A new study led by Break Through Cancer's Accelerating Glioblastoma (GBM) Therapies Through Serial Biopsies TeamLab has revealed that an engineered virus therapy, CAN-3110, triggered powerful immune responses deep inside glioblastoma tumors that were invisible to standard imaging like MRI, according to early analyses of two patients with recurrent GBM.

Published today in Science Translational Medicine, the research highlights the TeamLab's innovative approach of combining serial brain biopsies (tiny pieces of brain tissue removed while a patient is being treated) with advanced multi-omics analyses, can uncover dynamic changes in recurrent GBM. This is the first time scientists have mapped, in high-resolution, how oncolytic virus therapy reshaped the brain microenriornment in real-time.

The study involved two patients with recurrent GBM who underwent serial biopsies over four months of CAN-3110 treatment. Not only was the procedure well tolerated in these patients, but it also enabled an unprecedented level of insight into how tumors evolve during therapy. Standard practice is to not sample a patient's brain tumor as they undergo treatment rather, to sample only before treatment and then measure responses using MRI. But these findings suggest that this thinking and practice may need to change to revolutionize how patients can monitor their disease. Completion of the trial is required to help answer this question.

"This gives us a real-time window into what is happening inside the tumor," said Dr. E. Antonio Chiocca, MD, PhD, senior author and Chair of Neurosurgery at Brigham and Women's Hospital. "Instead of guessing whether a therapy is working based on scans alone, we now have a molecular map that shows how and where the immune system is engaging with the tumor."

While MRI scans appeared to show tumor growth, deeper molecular analyses told a different story. "This study challenges how we approach radiographic progression in glioblastoma" said Dr. Chiocca.

Using single-cell RNA sequencing, proteomics, immunopeptidomics, AI-enabled digital pathology and immune cell profiling, researchers observed a significant decrease in tumor cell content near virus injection sites. In their place, immune cells (including activated CD8+ and CD4+ T cells) proliferated and mounted targeted responses against both viral antigens and glioblastoma-specific markers. "In this study we show that the immune system can be trained to recognize and attack tumor cells through repeated viral therapy, even when imaging suggests failure."

The study is an early read-out of an ongoing clinical trial, part of a larger collaborative effort supported by Break Through Cancer, uniting researchers from leading institutions including Dana-Farber Cancer Institute, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Memorial Sloan Kettering Cancer Center, MIT's Koch Institute for Integrative Cancer Research, and The University of Texas MD Anderson Cancer Center to intercept and cure the deadliest cancers.

The findings signal a future model for glioblastoma research, one where treatment is guided not just by what can be seen on a scan, but by what is happening at the cellular and molecular level inside the tumor itself. This approach could help accelerate the development of more effective therapies for a disease for which progress has been stagnant for decades.

"This study reflects the kind of transformative collaboration Break Through Cancer was created to enable. It opens the door to smarter, more adaptive treatment strategies that can improve how new treatments are assessed and developed for patients with this devastating disease. "Tyler Jacks, PhD, President of Break Through Cancer.