Immunotherapy of Brain Tumors.

Abstract

Glioma is one of the most devastating cancers, affecting children and young adults, and associated with a very high morbidity and poor prognosis. The propensity of glioma cells to invade normal brain structures makes current treatments poorly efficient and new therapeutic strategies an urgent need. We now know that many of the rules governing immune responses in other tissues are also valid for the brain, providing solid scientific background for developing new strategies exploiting the immune system to fight brain tumors. Some vaccines use tumor-specific mutated peptides (EGFRvIII, IDH1 or personalized peptides), but most are tumor-associated or undefined tumor-derived peptides (tumor-eluted peptides, peptides predicted from tumor-associated proteins or bound to HSPPC-96 complexes), in some cases pulsed on dendritic cells. Cell therapy is less advanced but the first clinical trials exploring the safety of T cells with chimeric antigen receptors incorporating antibodies to EGFRvIII, IL-13Rα2 or Her2 are ongoing. Finally, various strategies designed at reshaping the glioma microenvironment are being tested, including TGFβ inhibition, Treg depletion and immune checkpoint blockade. Altogether, combining vaccines, cell therapy and reshaping of the tumor microenvironment will be the foundation for a new era of therapeutics for brain tumors.