Glioblastoma tumors were successfully infiltrated by investigational chimeric antigen receptor (CAR) therapy with an acceptable safety profile, according to phase 1 study results presented at the American Association for Cancer Research 2016 Annual Meeting.1
The T cells of the 9 patients treated so far were engineered in a laboratory to target a tumor-specific protein known as EGFRvIII, which is found in approximately 30% of GBM tumors. In contrast to other CAR therapies in which some healthy cells are also targeted, EGFRvIII is found only on tumor tissue. The hope with that targeting was to minimize side effects of the new therapy.
The safety profile was acceptable in all 9 patients treated so far. No clinical or laboratory signs were found of systemic cytokine release syndrome, which is a potentially serious toxicity that has occurred in participants of other CAR trials. One patient had a seizure (nonconvulsive status epilepticus) that was successfully treated with antiepileptic medications.
Significant expansion of CAR T-EGFRvIII occurred in all patients at 7 to 10 days after infusion. Tumors surgically removed from 5 patients at 6 to 120 days after infusion were examined pathologically and found to have focal areas with infiltration of both CAR-positive and CAR-negative T cells with signs of activation.
“One of the main questions in the field of T cell therapies is: can we make this work in solid tumors?” said Marcela Maus, MD, PhD, a former Penn faculty member who is now the director of Cellular Immunotherapy at the Massachusetts General Hospital Cancer Center and an assistant professor of medicine at Harvard Medical School in Boston. “The barriers to CAR T cells in solid tumors are identifying targets with acceptable safety profiles, proving that T cells can get out of the blood, and that they can successfully target the tumor cells expressing the antigen without being turned off by the tumor environment.
“Here, we demonstrated that targeting EGFRvIII has an acceptable safety profile, that CAR T cells do actually find their way and get into the tumor, even crossing the blood-brain barrier, and are able to eliminate the target.”
1. O’Rourke DM, Nasrallah MP, Morrissette J, et al. Phase I study of T cells redirected to EGFRvIII with a chimeric antigen receptor in patients with EGFRvIII+ glioblastoma. Presentation at: American Association for Cancer Research 2016 Annual Meeting, April 16-20, 2016; New Orleans, LA. Abstract LB-083.