Glioblastoma vaccine activates brain tumors in humans and dogs

Researchers from the University of Florida and biotech company iOncologi have developed a personalized mRNA-based cancer vaccine with an innovative "onion-like" delivery system. This vaccine has shown promise in prolonging survival in both dogs and humans with glioblastoma, according to a study published in Cell on May 1. The study involved seven years of research and included a phase 1 trial with four human patients and ten pet dogs suffering from spontaneous brain cancer.

The human participants in the study either survived or lived without disease longer than expected, although it is still too early to draw definitive conclusions about the vaccine's clinical impact. The median survival time for the dogs was 139 days, significantly longer than the typical 30- to 60-day survival period for such cases.

Eric Topol, M.D., Ph.D., founder of the Scripps Research Translational Institute, commented on the study's promising results. Topol noted that glioblastomas are among the most aggressive and fatal cancers and that the vaccine induced a notable anti-tumor response in the dogs.

This new vaccine is distinct from traditional mRNA vaccines, which usually deliver their genetic material in lipid nanoparticles targeting Toll-like receptors on immune cells. These receptors trigger the adaptive immune response. In contrast, the new vaccine encloses either mRNA or RNA derived from a patient’s tumor in RNA lipid particle aggregates (RNA-LPAs), which mimic a virus. These aggregates activate the RIG-I protein in stromal cells, found in various tissues and the tumor microenvironment. When injected into the bloodstream, this mechanism triggers a substantial release of cytokines, chemokines, dendritic cells, and lymphocytes, training the immune system to target and attack the cancer.

Elias Sayour, M.D., Ph.D., a senior author of the study, explained the reasoning behind this innovative design. By injecting clusters of these particles, the immune system is alerted more effectively compared to single particles, enhancing the immune response against cancer.

This approach addresses a major challenge in cancer vaccines: generating a robust immune response. UF researchers Christina von Roemeling, Ph.D., and John Ligon, M.D., emphasized that systemic injection of the vaccine, rather than direct injection into the skin, muscle, or tumor, ensures its distribution throughout the body, thereby activating a comprehensive immune response. They observed markers of immune activation in the blood within six hours and found that tumors became "hot," or penetrable by the immune system, within 48 hours.

Despite the promising results, there are potential side effects due to the heightened immune activity, which remain to be fully assessed as the study progresses. The researchers plan to expand their phase 1 study to include up to 24 pediatric and adult patients. Once the appropriate dosing is established, a phase 2 trial involving 25 pediatric patients is planned. Additionally, they hope to explore the vaccine's potential in combination with other immunotherapies, as preliminary evidence suggests that such an approach could be beneficial.

Sayour expressed optimism about the vaccine's future, suggesting that it could potentially enhance the effectiveness of existing immunotherapies.