Effectiveness and Safety of mRNA Vaccines in the Therapy of Glioblastoma

Abstract

Glioblastoma (GBM) is the most common and most malignant primary brain tumor, presenting significant treatment challenges due to its heterogeneity, invasiveness, and resistance to conventional therapies. Despite aggressive treatment protocols, the prognosis remains poor, with a median survival time of approximately 15 months. Recent advancements in mRNA vaccine technology, particularly the development of lipid nanoparticles (LNPs), have revitalized interest in mRNA-based therapies. These vaccines offer unique advantages, including rapid production, personalization based on tumor-specific mutations, and a strong induction of both humoral and cellular immune responses. mRNA vaccines have demonstrated potential in preclinical models, showing significant tumor regression and improved survival rates. Early-phase clinical trials have indicated that mRNA vaccines are safe and can induce robust immune responses in GBM patients. Combining mRNA vaccines with other immunotherapeutic approaches, such as checkpoint inhibitors, has shown synergistic effects, further enhancing their efficacy. However, challenges such as optimizing delivery systems and overcoming the immunosuppressive tumor microenvironment remain. Future research should focus on addressing these challenges and exploring combination therapies to maximize therapeutic benefits. Large-scale, randomized clinical trials are essential to validate the efficacy and safety of mRNA vaccines in GBM therapy. The potential to reshape the tumor microenvironment and establish long-term immunological memory underscores the transformative potential of mRNA vaccines in cancer immunotherapy.

Keywords: cancer immunotherapy; glioblastoma; lipid nanoparticles; mRNA vaccines; tumor microenvironment.

Figure 1

Mechanism of mRNA vaccine action in antigen-presenting cells (APCs) for glioblastoma treatment. This figure illustrates the intracellular processing and presentation of antigens from mRNA vaccines by antigen-presenting cells (APCs) and the subsequent activation of T cells. The mRNA vaccine enters the APC through endocytosis, depicted by the mRNA vaccine enclosed in lipid nanoparticles being taken up by the APC. Once inside the cytoplasm, the mRNA is released and translated by ribosomes into the encoded antigen protein. The synthesized antigen is then processed by the proteasome, which degrades the protein into smaller peptide fragments known as epitopes. Some of these epitopes are loaded onto major histocompatibility complex (MHC) class I molecules and transported to the cell surface, where they can be recognized by CD8+ T cells. This pathway is crucial for the activation of cytotoxic T lymphocytes (CTLs), which can directly kill glioblastoma cells. Other epitopes are loaded onto MHC class II molecules and transported to the cell surface to be recognized by CD4+ T helper cells. This interaction is essential for the activation and proliferation of helper T cells, which aid in orchestrating the immune response by stimulating other immune cells, including B cells and CTLs. The interaction between the MHC–epitope complex and the T cell receptor on CD4+ and CD8+ T cells leads to their activation. Activated CD8+ T cells can target and destroy glioblastoma cells presenting the specific antigen, while CD4+ T cells provide critical support to sustain and enhance the immune response. This comprehensive pathway highlights the critical steps involved in the immune response elicited by mRNA vaccines and their potential application in glioblastoma treatment by harnessing the body’s own immune system to target and eliminate cancer cells. Figure 1 was drawn in part using images from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 4.0 License.