Recent Advances in Brain Tumor Vaccines: With a Special Focus on Glioblastoma Treatment—A Systematic Review

Abstract Glioblastoma is one of the most aggressive malignant brain tumors with a poor prognosis despite surgery, radiation, and chemotherapy. Immunotherapy, particularly vaccines, is becoming increasingly promising in enhancing clinical outcomes. This review aims to summarize advancements and associated limitations in brain tumor vaccine development and focuses on vaccine-based approaches for glioblastoma, aiming to bridge current evidence with future strategies toward standardization. To systematically evaluate and compare recent advances in brain tumor vaccines, with a particular focus on glioblastoma, by critically analyzing vaccine platforms, mechanisms of action, and phase-wise clinical outcomes reported across heterogeneous clinical trials. A systematic review was conducted in accordance with PRISMA guidelines. The literature searches were performed on PubMed, Google Scholar, and ClinicalTrials.gov for studies published between 2010 and 2024. Search terms included “Brain tumor vaccines” and “Glioblastoma vaccines.” Inclusion and exclusion criteria were created for the selection of studies. The review identified 71 articles meeting the inclusion criteria. These included 4 randomized controlled trials, 22 early-phase trials (8 Phase I, 11 Phase II, 3 Phase III trials), and 43 systematic reviews. Peptide vaccines targeted tumor-specific antigens, dendritic cell vaccines enhanced antigen presentation, and mRNA-based vaccines offered novel platforms for antigen delivery. The DCVax-L and EGFR mutation-based vaccines have demonstrated extended survival but also have limitations like tumor heterogeneity and antigen escape. Brain tumor vaccines for glioblastoma suffer from challenges due to tumor heterogeneity and limited clinical efficacy. Many novel options are upcoming; however, a proven vaccine is currently lacking. The future is open for personalized and multitargeted therapies.