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HER2-Specific CAR T-Cell Therapy Active in Progressive Glioblastoma

Administration of autologous HER2-specific CAR-modified virus specific T Cells was safe and had clinical benefit for some patients with progressive glioblastoma, a disease with limited effective therapeutic options.

Administration of autologous HER2-specific chimeric antigen receptor (CAR)-modified virus specific T Cells (VSTs) was safe and had clinical benefit for some patients with progressive glioblastoma, a disease with limited effective therapeutic options.

Results of a small phase I study of this monotherapy were published in JAMA Oncology, by Nabil Ahmed, MD, MPH, of Baylor College of Medicine in Houston, and colleagues.

“CAR T-cell therapies are an attractive strategy to improve the outcomes for patients with glioblastoma,” they wrote. “In our study, we infused HER2-CAR VSTs intravenously because T cells can travel to the brain after intravenous injections, as evidenced by clinical responses after the infusion of tumor-infiltrating lymphocytes for melanoma brain metastasis and by detection of CD19-CAR T cells in the cerebrospinal fluid of patients with B-precursor leukemia.”

The study included 17 patients with progressive HER2-positive glioblastoma (10 patients aged 18 or older; 7 patients younger than 18). Patients were given one or more infusions of autologous VSTs specific for cytomegalovirus, Epstein-Barr virus, or adenovirus and genetically modified to express HER2-CARs. Six patients were given multiple infusions.

Infusions were well tolerated with no dose limiting toxicities presenting. Two patients had grade 2 seizures and/or headaches, which the researchers wrote were “probably related to the T-cell infusion.”

Although HER2-CAR VSTs did not expand, they were detected in the peripheral blood for up to 12 months after the infusion.

“Although we did not observe an expansion of HER2-CAR VSTs in the peripheral blood, T cells could have expanded at glioblastoma sites. At 6 weeks after T-cell infusion, the MRI scans of patients 3, 7, 10, 16, and 17 showed an increase in peritumoral edema,” the researchers wrote. “Although these patients were classified as having a progressive disease, it is likely that the imaging changes for some of these patients were due to inflammatory responses, indicative of local T-cell expansion, especially since these patients survived for more than 6 months.”

Only 16 of the 17 patients were evaluable for response. Patients underwent brain MRI 6 weeks after T-cell infusion. One patient had a partial response for longer than 9 months and seven patients had stable disease for between 8 weeks to 29 months. Three patients with stable disease are alive without any evidence of progression from 24 to 29 months of follow-up. Eight patients progressed after the infusion.

The median overall survival was 11.1 months from the first T-cell infusion and 24.5 months from diagnosis.

The researchers noted that the inclusion of children in the study, who have a better prognosis than adults, may have affected the results; however, “there was no significant difference between the survival probability for children and that for adults in this clinical study.”