Autologous T cell Therapy for Cytomegalovirus as a Consolidative Treatment for Recurrent Glioblastoma

Glioblastoma multiforme (GBM) is one of the most aggressive human brain malignancies. Even with optimal treatment, median survival is less than six months for patients with recurrent GBM. Immune-based therapies have the potential to improve patient outcome by supplementing standard treatment. Expression of human cytomegalovirus (CMV) antigens in GBM tissues provides the unique opportunity to target viral antigens for GBM therapy. Here we report findings of a formal clinical assessment of safety and potential clinical efficacy of autologous CMV-specific T cell therapy as a consolidative treatment for recurrent GBM. From a total of 19 recurrent GBM patients, CMV-specific T cells were successfully expanded from 13 patients (68.4%) and 11 of whom received up to four T cell infusions. Combination therapy based on T cell infusion and chemotherapy was well tolerated and we detected only minor adverse events. The overall survival of these patients since first recurrence ranged from 133 to 2428 days with a median overall survival of 403 days. Most importantly, four out of 10 patients that completed the treatment remained progression free during the study period. Furthermore, molecular profiling of CMV-specific T cell therapy from these patients revealed distinct gene expression signatures which correlated with their clinical response. Our study suggests that that a combination therapy with autologous CMV specific T cells and chemotherapy is a safe novel treatment option and may offer clinical benefit for recurrent GBM patients.