Last updated 4/27/25
Glioblastoma (GBM) creates an immune-suppressive micro-environment that allows it to grow unchecked. Immunotherapy aims to tip the balance back toward immune control by (a) exposing the tumor to the immune system and (b) releasing the molecular brakes that stop T cells from attacking.
Vaccines such as DCVax-L, SurVaxM, NeoVax and Gliovac train dendritic cells and T cells to recognise tumour antigens. For full details see our dedicated page: Therapeutic Vaccines for Glioblastoma.
T cells have built-in "checkpoints"-molecules such as PD-1 and CTLA-4-that act like ID badges. When these badges engage their ligands (PD-L1, PD-L2 or CD80/CD86) on other cells they send a stop signal that prevents collateral damage to healthy tissue. GBM exploits this by up-regulating PD-L1 on tumour and myeloid cells, effectively hiding in plain sight.
Checkpoint inhibitors are monoclonal antibodies that block the stop-signal, allowing T cells to remain active. The main drugs being tested in GBM are:
Ongoing studies focus on combinations: checkpoint inhibitor + vaccine, TTFields, oncolytic virus or radiation to convert "cold" tumours into "hot" ones that respond better to blockade.
Viruses can be engineered to selectively infect GBM cells and spark an in-situ vaccine effect. Examples include:
Chimeric Antigen Receptor (CAR) T cells are patient T cells re-programmed to express receptors that bind GBM surface markers. Targets in clinical testing include EGFRvIII, IL13Rα2, HER2 and B7-H3.
Poly-ICLC (Hiltonol) is a synthetic double-stranded RNA that activates TLR-3 and MDA-5, driving type-I interferon release. Used as:
Gene therapy delivers genetic payloads directly into the tumour to either kill cells or enhance immune visibility. Strategies include IL-12 gene transfer (Ad-RTS-hIL-12 + veledimex, NCT04006119) and herpes-thymidine-kinase suicide gene combined with valganciclovir (Toca 511 studies).
Modality | Trial ID | Title / Notes |
---|---|---|
Checkpoint inhibitor + TTFields | NCT03233152 | Pembrolizumab combined with Tumor Treating Fields for recurrent GBM |
Oncolytic virus | NCT05076513 | Lerapolturev (PVSRIPO) + pembrolizumab - LUMINOS-101 |
CAR-T (IL13Rα2) | NCT02208362 | Re-dosing intraventricular IL13Rα2 CAR-T cells |
Poly-ICLC + peptide vaccine | NCT04329065 | Multipeptide vaccine (IMA950) with Poly-ICLC in newly diagnosed GBM |
IL-12 gene therapy | NCT04006119 | Ad-RTS-hIL-12 plus veledimex for recurrent GBM |
No single immunotherapy has yet delivered a definitive survival advantage in unselected GBM patients, but signals of long-term survival in small sub-groups suggest that the right combination and right patient selection could transform outcomes. Keeping informed about trial options and emerging biomarkers (for example MGMT status, T-cell inflamed gene signature or CSF-ctDNA) is essential.