What is the role of vaccine therapy in the treatment of glioblastoma multiforme (GBM)?

Updated: Jul 28, 2021
  • Author: Jeffrey N Bruce, MD; Chief Editor: Herbert H Engelhard, III, MD, PhD, FACS, FAANS  more...
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Answer

Vaccines being studied for treatment of glioblastoma include modified polio vaccine and cytomegalovirus (CMV) vaccine.

Modified polio vaccine therapy

The poliovirus receptor CD155 is broadly upregulated on the surface of malignant solid tumors, and a preliminary study of intratumoral infusion of a modified poliovirus vaccine has demonstrated benefit in some cases of recurrent  malignant glioma. In a dose-finding and toxicity study, 61 patients with recurrent supratentorial WHO grade IV malignant glioma received seven doses of a live attenuated poliovirus type 1 vaccine with its cognate internal ribosome entry site replaced with that of human rhinovirus type 2. The recombinant nonpathogenic polio–rhinovirus chimera was infused into the glioma via an implanted catheter. [117]

In contrast to overall survival rates in a historical control group, which declined steadily to 14% at 24 months and 4% at 36 months, overall survival in the study patients stabilized at 21% at 24 months, remaining at that rate through 36 months. Adverse events that affected more than 20% of the study patients in the dose-expansion phase included headache (52%), hemiparesis (50%), seizure (45%), dysphasia (28%), and cognitive disturbance (25%). [117]

Cytomegalovirus vaccine

Approximately 90% of glioblastomas express CMV proteins, and Batich et al have reported benefit with a dendritic cell vaccine targeting CMV antigen pp65, using CMV as a proxy for glioblastoma. [118] Patients are first treated with dose-intensified temozolomide, as the temozolomide induces lymphopenia, which provides an opportunity to retrain the immune system.

In a study of 11 patients with newly diagnosed glioblastoma received temozolomide, 100 mg/m2/d × 21 days per cycle, and at least three pp65-directed vaccines admixed with granulocyte-macrophage colony-stimulating factor on day 23 ± 1 of each cycle. Despite increased proportions of regulatory T cells (Tregs), median progression-free survival was 25.3 months and overall survival was 41.1 months; three patients remained progression-free more than 7 years after diagnosis. [118]


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