Tumour vaccines show potential for glioma treatment
07 Aug 2025
Elaine Tan
Elaine Tan
Research on vaccine therapies for glioma has advanced markedly in recent years, with >100 glioma vaccine clinical trials currently ongoing worldwide, according to a recent update review.
Among the ongoing clinical trials are phase II and III studies on dendritic cell (DC) vaccines, phase I and II studies on peptide vaccines, and a few in various phases on personalized cellular vaccines, indicating significant potential of vaccine therapies in glioma treatment. [Front Oncol 2025;15:1613332]
Gliomas account for >50 percent of central nervous system (CNS) malignant tumours, and recurrence and mortality rates are high. Effective treatment of gliomas remains a therapeutic challenge due to the complex molecular landscape, high heterogeneity, and immunosuppressive tumour microenvironment. [Neuro Oncol 2024;2(S6):iv1-iv85; Front Oncol 2025;15:1613332]
The blood-brain barrier (BBB) also presents a major challenge in the clinical application of glioma vaccines, which require efficient delivery of antigens, adjuvants, and immune cells to activate the immune system within the tumour microenvironment. New strategies and delivery systems such as lipid nanoparticles and focused ultrasound have shown potential in overcoming the BBB. [Nat Med 2025;31:1557-1566; Nano Lett 2025;25:800-810; Transl Neurodegener 2022;11:57]
Tumour vaccines, biologics designed to stimulate or restore the immune system’s ability to recognize and destroy cancer cells, are primarily used as adjuvant therapy following radiotherapy, chemotherapy, or surgical resection, as part of multimodal strategy to improve clinical outcomes. They can be categorized into three main types based on the source of the tumour antigen expressed: protein/peptide vaccines, DC vaccines, and nucleic acid vaccines (including DNA and RNA vaccines). [Front Oncol 2025;15:1613332]
Notably, a landmark phase III study showed that adding autologous tumour lysate–loaded DC vaccination (DCVax-L) to standard of care (SoC) treatment was associated with a clinically meaningful and statistically significant improvement in median overall survival for patients with newly diagnosed glioblastoma (nGBM) as well as recurrent GBM (rGBM) compared with matched, contemporaneous external controls treated with SoC (nGBM: 19.3 vs 16.5 months from randomization; p=0.002) (rGBM: 13.2 vs 7.8 months from relapse; p<0.001). Survival rate was 13.0 vs 5.7 percent at 60 months for the nGBM group, and 11.1 vs 5.1 percent at 30 months (from recurrence) for the rGBM group. [JAMA Oncol 2023;9:112-121]
“When combined with SoC, this personalized immunotherapy achieved unprecedented outcomes, becoming the first intervention in two decades to improve survival in newly diagnosed glioma patients, and the first in three decades to show significant survival extension in recurrent glioma, while maintaining an excellent safety profile,” wrote the authors. [Front Oncol 2025;15:1613332]
Personalized neoantigen vaccines, which target mutations unique to a patient’s tumour, could revolutionize glioma therapy by enabling highly specific treatment. Personalized neoantigens are immunogenic mutations uniquely expressed in individual patients. These neoantigens are absent in normal tissues and are not subject to central or peripheral immune tolerance mechanisms. Identifying personalized neoantigens is a critical step toward achieving individualized therapy for glioma patients.
“While glioma vaccines remain in early stages of development, ongoing clinical trials and technological advancements offer hope for novel therapeutic avenues. The integration of immunotherapy into standard glioma treatment regimens, particularly through synergistic combination therapies, is poised to become a cornerstone in managing this aggressive disease,” the authors concluded.
Among the ongoing clinical trials are phase II and III studies on dendritic cell (DC) vaccines, phase I and II studies on peptide vaccines, and a few in various phases on personalized cellular vaccines, indicating significant potential of vaccine therapies in glioma treatment. [Front Oncol 2025;15:1613332]
Gliomas account for >50 percent of central nervous system (CNS) malignant tumours, and recurrence and mortality rates are high. Effective treatment of gliomas remains a therapeutic challenge due to the complex molecular landscape, high heterogeneity, and immunosuppressive tumour microenvironment. [Neuro Oncol 2024;2(S6):iv1-iv85; Front Oncol 2025;15:1613332]
The blood-brain barrier (BBB) also presents a major challenge in the clinical application of glioma vaccines, which require efficient delivery of antigens, adjuvants, and immune cells to activate the immune system within the tumour microenvironment. New strategies and delivery systems such as lipid nanoparticles and focused ultrasound have shown potential in overcoming the BBB. [Nat Med 2025;31:1557-1566; Nano Lett 2025;25:800-810; Transl Neurodegener 2022;11:57]
Tumour vaccines, biologics designed to stimulate or restore the immune system’s ability to recognize and destroy cancer cells, are primarily used as adjuvant therapy following radiotherapy, chemotherapy, or surgical resection, as part of multimodal strategy to improve clinical outcomes. They can be categorized into three main types based on the source of the tumour antigen expressed: protein/peptide vaccines, DC vaccines, and nucleic acid vaccines (including DNA and RNA vaccines). [Front Oncol 2025;15:1613332]
Notably, a landmark phase III study showed that adding autologous tumour lysate–loaded DC vaccination (DCVax-L) to standard of care (SoC) treatment was associated with a clinically meaningful and statistically significant improvement in median overall survival for patients with newly diagnosed glioblastoma (nGBM) as well as recurrent GBM (rGBM) compared with matched, contemporaneous external controls treated with SoC (nGBM: 19.3 vs 16.5 months from randomization; p=0.002) (rGBM: 13.2 vs 7.8 months from relapse; p<0.001). Survival rate was 13.0 vs 5.7 percent at 60 months for the nGBM group, and 11.1 vs 5.1 percent at 30 months (from recurrence) for the rGBM group. [JAMA Oncol 2023;9:112-121]
“When combined with SoC, this personalized immunotherapy achieved unprecedented outcomes, becoming the first intervention in two decades to improve survival in newly diagnosed glioma patients, and the first in three decades to show significant survival extension in recurrent glioma, while maintaining an excellent safety profile,” wrote the authors. [Front Oncol 2025;15:1613332]
Personalized neoantigen vaccines, which target mutations unique to a patient’s tumour, could revolutionize glioma therapy by enabling highly specific treatment. Personalized neoantigens are immunogenic mutations uniquely expressed in individual patients. These neoantigens are absent in normal tissues and are not subject to central or peripheral immune tolerance mechanisms. Identifying personalized neoantigens is a critical step toward achieving individualized therapy for glioma patients.
“While glioma vaccines remain in early stages of development, ongoing clinical trials and technological advancements offer hope for novel therapeutic avenues. The integration of immunotherapy into standard glioma treatment regimens, particularly through synergistic combination therapies, is poised to become a cornerstone in managing this aggressive disease,” the authors concluded.