Malignant Glioma Immunotherapy: A Peptide Vaccine from Bench to Bedside

Abstract

Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively active, mutant form of the wild-type receptor. It is expressed frequently in malignant glioma cells, yet absent in all normal tissues. EGFRvIII arises from an in-frame deletion, the translation of which incidentally alters the extracellular domain of the receptor. This unique motif makes EGFRvIII an especially attractive target for an immunotherapeutic approach. Our laboratory has developed and tested a novel peptide vaccine based on this mutation, and has demonstrated the ability to elicit EGFRvIII-specific immune responses in both preclinical and early clinical models using this vaccine. Furthermore, we have shown that, for patients who bear EGFRvIII-expressing gliomas, vaccination-induced humoral and delayed-type hypersensitivity responses are associated with improved survival, even in the context of concurrent chemotherapy-induced lymphodepletion.