Cell therapies against brain tumors: Clinical development and emerging prospects

Malignant brain tumors, particularly glioblastoma multiforme (GBM), are aggressive and fatal cancers. The clinical efficacy of current standard-of-care treatments against brain tumors has been minimal, with no significant improvement over the past 30 years. Driven by the success of chimeric antigen receptor (CAR)-T cells in the clinic for treating certain types of cancer, adoptive cell therapies have been of interest as a hopeful therapeutic modality for brain tumors. Clinical trials of GBM-targeting cell therapies, including CAR-T cells, have been initiated; however, none of them have been approved yet, and new challenges have emerged from the completed clinical trials. These issues are being addressed in ongoing clinical trials and recent preclinical research efforts. Herein, we present an overview of the clinical landscape of cell therapies against brain tumors. We analyze past and active 203 clinical trials focusing on cell therapies for brain tumors, discuss limitations for their clinical translation, and highlight emerging approaches to address these challenges. In addition, we review select preclinical studies that show promise to improve the therapeutic efficacy of therapeutic cells on brain tumors and discuss future prospects.