Overcoming barriers in glioblastoma: The potential of CAR T cell immunotherapy

Glioblastoma (GBM), the most aggressive and lethal primary brain tumor, is characterized by its high rate of growth, high genetic diversity, and resistance to conventional therapies. Chimeric antigen receptor (CAR) T cell immunotherapy has emerged as a promising treatment option for a variety of cancers, including GBM. However, CAR T therapy use in GBM is very challenging due to the unique challenges posed by the brain tumor microenvironment, including immune suppression, antigen heterogeneity, poor CAR T cell trafficking, and the blood-brain barrier (BBB). Advances in CAR T cell engineering, antigen screening, targeted administration, image-guided CAR-T therapy and combination therapies are transforming immunotherapy for GBM.AI-driven CAR T immunotherapy optimizes GBM treatment by enhancing target identification, therapy customization, and efficacy monitoring. This review aims to highlight the challenges hindering the success of CAR T cell therapy in glioblastoma and explore innovative strategies to enhance its efficacy, ultimately paving the way for more effective and durable treatment options for glioblastoma. We hope this review will stimulate interest among researchers and expedite the clinic translation of CAR T therapy of glioblastoma.