Researchers at the University of Pennsylvania have developed a personalized immune therapy that redirects T cells to seek and destroy a type of glioblastoma, or brain tumor.
About 30 percent of glioblastoma patients have tumors with a mutation in a growth receptor called EGFR.
“It makes the tumor cells grow,” said Marcela Maus, a physician-scientist at Penn and senior author of the new study. “Patients that have that kind of mutation tend to have a worse prognosis than patients who don’t have it.”
But because the mutation is specific to the tumor — and can serve as a sort of beacon to properly designed immune cells — it might actually be this cancer’s Achilles’ heel.
The treatment involves taking patients’ T cells, then inserting a new gene that allows the cells to recognize the mutant protein. After about a week in the lab, the cells can be reinfused and begin their task of zeroing in on and eliminating cells with the mutation.
The technology is similar to other efforts at the University of Pennsylvania to reprogram T cells to treat leukemia, but this is the first time the team has applied the approach to solid tumors.
“It’s taking an antibody, which is typically a kind of molecule that’s circulating around in the blood,” said Maus. “And it’s fusing it to proteins that will cross the membrane and that then will signal to T cells to replicate and kill.”
Much of the team’s early efforts have focused on making sure the newly directed T cells only target the brain tumor, Maus said. So far, there’s no sign they will also attack the many healthy cells that express the normal version of the growth receptor.
In mouse models of the disease, the group found that the tweaked T cells successfully shrank tumors and led to longer survival. The results were published Wednesday in the journal Science Translational Medicine.
In collaboration with the pharmaceutical company Novartis, Penn has begun a phase I clinical trial to test the safety of the approach in people.