Entering a new phase in cell therapy for glioblastoma

After a lot of frustration and too few successes, the cell therapy field has reached a new phase in its pursuit for better treatments for the deadly brain cancer glioblastoma multiforme (GBM). For decades, treatment approaches using surgery, chemotherapy, and radiation have sometimes helped to slow tumors’ growth, but the disease has almost always recurred and proved lethal. For that reason, over the last decade, Donald M. O’Rourke, director of the Glioblastoma Translational Center of Excellence at Penn Medicine, and others began to explore cellular immunotherapies—similar to those developed at Penn Medicine and approved for certain blood cancers—as a potential better option for these brain tumors.

Grid of eight brain scans.

This decade-long focus in the lab and clinic, heightened by President Biden’s Moonshot initiative over the last five years, has helped answer questions about the tumor itself and previous therapies’ shortcomings. Now, researchers are on the cusp of delivering the next generation of chimeric antigen receptor cellular therapies (CARs) that could instill fresh hope for patients with GBM and other types of solid tumors.

“The amount and richness of GBM research is dramatically better than it was,” says O’Rourke, who also serves as the John Templeton, Jr., M.D. Professor in Neurosurgery in the Perelman School of Medicine. “And when there is increased work and scholarship being done in the field, it will get clinically translated and there will be an improvement.”

At Penn, a leader in GBM cellular therapies since the early days of this technology, a new CAR cell therapy could find its way into clinical trials by next year in collaboration with Tmunity Therapeutics, a Philadelphia-based biotherapeutics developer. O’Rourke and his team believe this “dual target” CAR could accomplish what its predecessors couldn’t: withstand a hostile tumor microenvironment and more precisely target and fight the tumor unhindered.

The timing is a tough reminder just how hard that has been for any treatment. Fifty years after the architects of the National Cancer Act signed it into law and more than 200 years since GBM was first reported, the median survival time is only 15 months, even after today’s aggressive treatments with chemotherapy and radiation. The five-year survival rate remains at just 10%, and nearly everyone who battles the disease loses.

“This is important for two reasons: for the field, which is really filled with desperation right now and continued setbacks,” O’Rourke says. “And for desperate patients who have a disease that still has no standard of care, which is an illustration of how bad things have been.”

Read more at Penn Medicine News.