Despite decades of research and the best up-to-date treatments, grade 4 Glioblastoma (GBM) remains uniformly fatal with a patient median overall survival of less than 2 years. Recent advances in immunotherapy have reignited interest in utilizing immunological approaches to fight cancer. However, current immunotherapies have so far not met the anticipated expectations, achieving modest results in their journey from bench to bedside for the treatment of GBM. Understanding the intrinsic features of GBM is of crucial importance for the development of effective antitumoral strategies to improve patient life expectancy and conditions. In this review, we provide a comprehensive overview of the distinctive characteristics of GBM that significantly influence current conventional therapies and immune-based approaches. Moreover, we present an overview of the immunotherapeutic strategies currently undergoing clinical evaluation for GBM treatment, with a specific emphasis on those advancing to phase 3 clinical studies. These encompass immune checkpoint inhibitors, adoptive T cell therapies, vaccination strategies (i.e., RNA-, DNA-, and peptide-based vaccines), and virus-based approaches. Finally, we explore novel innovative strategies and future prospects in the field of immunotherapy for GBM.
Keywords: CAR-T cell therapy; DNA/RNA vaccines; GBM; GBM immunosuppressive tumor microenvironment; adoptive cell therapy; immune checkpoint therapy; immunotherapy; oncolytic virotherapy; vaccination therapy.