Abstract
Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. Current treatment options for GBM include surgical resection, radiation, and chemotherapy, which predominantly only slow cancer growth and reduce symptoms, resulting in a 5-year survival rate of no more than 10%. Chimeric antigen receptor (CAR)-T cell therapy is a new class of cellular immunotherapies that has made great progress in the treatment of malignant tumors. Human epidermal growth factor receptor 2 (HER2) is over-expressed in GBM, and may provide a potential therapeutic target for GBM treatment. In this study, we constructed third-generation CAR-T cells targeting the HER2 antigen in GBM. HER2-CAR-T cells showed effective antitumor abilities both in vitro and in vivo. Furthermore, HER2-specific CAR-T cells exhibited strong cytotoxicity and cytokine-secreting ability against GBM cells in vitro. Anti-HER2 CAR-T cells also exerted increasing cytotoxicity from low to high effector-to-target (E: T) ratios. Importantly, anti-HER2 CAR-T cells delivered by peritumoral injection successfully stunted tumor progression in vivo. Moreover, peritumoral intravenous administration of anti-HER2 CAR-T exhibited a therapeutic improvement against GBM cells compared with intravenous administration. In conclusion, our studies show that HER2 CAR-T cells represent an emerging immunotherapy for the treatment of GBM.