DDDR-16. A comprehensive review of immunotherapeutic modalities in glioblastoma: mechanisms, efficacy, and safety considerations

Abstract INTRODUCTION Glioblastoma multiforme (GBM), the most aggressive primary brain neoplasm, has a median survival of 15 months despite current standard treatment. GBM’s characteristic heterogeneous and immunosuppressive microenvironment presents unique challenges to immune-based interventions. Immunotherapy, particularly in combination with other treatments, holds promise for glioblastoma, warranting investigation into which regimens are most promising in providing clinical benefits. Objective: To determine how immunotherapeutic strategies address the unique challenges of GBM and evaluate their prospects for improving clinical outcomes. METHODS A comprehensive search across PubMed, Embase, Scopus, Cochrane, and Web of Sciences was conducted based on PRISMA guidelines for publications examining the efficacy of immunotherapy regimens in treating GBM. RESULTS 78% of articles studied the most common approaches: immune checkpoint inhibitors (ICIs), CAR T-cell therapy, and/or vaccines. 34% found that ICIs are moderately successful treating those with hypermutated tumors or higher PD-L1 expression, but they do not significantly improve survival as a monotherapy. Single peptide vaccines demonstrated mixed results; 71% of correlated trials failed to demonstrate survival benefits. Perceived obstacles in the success of immunotherapy include the heterogeneous and immunosuppressive tumor environment, the blood-brain barrier, low tumor mutation burden, antigen escape, and T cell exhaustion. Recent breakthroughs have begun overcoming these barriers. Early-phase trials of oncolytic viruses have shown immune activation and prolonged survival, while dendritic cell vaccines have been correlated to improved survival in phase II and III trials. The promising potential of CAR T-cell therapy, which remains experimental, was mentioned in 13% of papers. 89% of authors cited combination or multi-target immunotherapies as correlated with strong immunogenicity, reduced off-target toxicity, prolonged survival, and tumor reduction. CONCLUSION Although various approaches are being developed for GBM treatment, combination immune therapies targeting different mechanisms of actions are most promising in overcoming existing challenges. These findings can inform the development of effective, personalized therapies.