Immunotherapy Strategies for Glioblastoma Treatment

Glioblastoma (GBM) remains one of the most aggressive primary brain malignancies, exhibiting profound resistance to conventional surgery, radiotherapy and chemotherapy. Immunotherapy seeks to harness the patient’s own immune system to recognise and eliminate malignant cells. Strategies include immune checkpoint inhibitors that release inhibitory brakes on T cells, oncolytic viruses that selectively infect and lyse tumour cells while stimulating local immunity, therapeutic vaccines that prime T cells against tumour-specific neoantigens, and adoptive cell therapies such as chimeric antigen receptor (CAR) T cells engineered to target GBM antigens. A critical challenge is the highly immunosuppressive tumour microenvironment, marked by regulatory T cells, myeloid-derived suppressor cells and inhibitory cytokines. Overcoming the blood–brain barrier to achieve sufficient intratumoral delivery of biologics is equally vital. Recent advances have revealed that combinatorial approaches—pairing checkpoint blockade with oncolytic virotherapy, vaccine regimens or phagocytosis modulators—can synergise innate and adaptive arms of immunity. Progress in biomaterial carriers and cell engineering is paving the way towards treatments that elicit durable immune memory and improved clinical outcomes.

Research from Nature Portfolio

Recent clinical evaluation of intratumoral delivery of an oncolytic adenovirus followed by systemic anti-PD-1 blockade has demonstrated safety and signs of durable benefit in a subset of patients with recurrent GBM. Although the objective response rate remained modest, overall survival at one year exceeded historical controls and detailed immunophenotyping linked tumour infiltration by cytotoxic lymphocytes with clinical benefit. In parallel, a first-in-human vaccine trial targeting the mutant IDH1(R132H) neoantigen in newly diagnosed astrocytoma patients proved safe and highly immunogenic. More than 90% of vaccinated individuals mounted specific helper T cell responses across diverse MHC backgrounds. Impressively, progression-free survival at two years was markedly higher among responders, and episodes of pseudoprogression correlated with vigorous intratumoral inflammatory reactions, underscoring the capacity of mutation-specific vaccines to generate local antitumour immunity and long-term immune surveillance.

Immunotherapy Strategies for Glioblastoma Treatment publication trend

The graph below shows the total number of articles in immunotherapy strategies for glioblastoma treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Immune checkpoint inhibitor: A monoclonal antibody that blocks regulatory pathways (for example PD-1/PD-L1) to enhance T cell-mediated tumour killing.

Oncolytic virus: A genetically modified virus that selectively infects and destroys tumour cells while promoting an antitumour immune response.

Chimeric antigen receptor (CAR) T cell: A patient’s T lymphocyte engineered to express a synthetic receptor targeting specific tumour antigens.

Tumour microenvironment: The complex milieu of immune cells, stromal cells, cytokines and extracellular matrix surrounding a tumour.

Neoantigen: A tumour-specific antigen arising from somatic mutations, recognised as non-self by the immune system.

References

1. Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial. Nature Medicine (2023).
2. Bioengineer mesenchymal stem cell for treatment of glioma by IL‐12 mediated microenvironment reprogramming and nCD47‐SLAMF7 mediated phagocytosis regulation of macrophages. Exploration (2024).
3. Immunotherapy for glioblastoma: current state, challenges, and future perspectives. Cellular & Molecular Immunology (2024).
4. A vaccine targeting mutant IDH1 in newly diagnosed glioma. Nature (2021).