Immunotherapies for brain cancer: from preclinical models to human trials

Abstract

Glioblastoma Multiforme (GBM) is the most common and aggressive primary brain tumor. Every year ~22,000 patients are diagnosed with GBM in the US, and less than 5% survive 5 years post-diagnosis. Thus, novel therapeutic approaches are urgently needed to improve the outcome in these patients. Immunotherapy has the potential of stimulating the immune system to eliminate GBM cells that might have spread throughout the brain. Here we will discuss the latest advances in preclinical immunotherapy for glioma, which involve the local delivery of pro-inflammatory cytokines, such as Flt3L, Type I IFNs, IL-2, IL-4, and IL-12 using gene therapy vectors and neural stem cells, or the blockade of immune-suppressive mediators such as TGF-beta, FasL and phosphorylated STAT3. Novel immunotherapeutic approaches have also been assessed in clinical trials implemented in GBM patients. These involve the systemic or local adoptive transfer of autologous immune cells activated ex vivo back into the patient, and the administration of dendritic cell vaccines loaded with tumor peptides or cells, which induce active immunity against GBM. Preclinical and clinical findings so far indicate that immunotherapy improves anti-tumor immunity in preclinical GBM models and patients, which makes it a valuable adjuvant in the treatment of GBM.