Targeting EGF receptor variant III: tumor-specific peptide vaccination for malignant gliomas

Abstract

Glioblastoma multiforme (GBM) is the most common and deadly of the human brain cancers. The EGF receptor is often amplified in GBM and provides a potential therapeutic target. However, targeting the normal receptor is complicated by its nearly ubiquitous and high level of expression in certain tissues. A naturally occurring deletion mutant of the EGF receptor, EGFRvIII, is a constitutively active variant originally identified in a high percentage of brain cancer cases, and more importantly is rarely found in normal tissue. A peptide vaccine, rindopepimut (CDX-110, Celldex Therapeutics), is directed against the novel exon 1–8 junction produced by the EGFRvIII deletion, and it has shown high efficacy in preclinical models. Recent Phase II clinical trials in patients with newly diagnosed GBM have shown EGFRvIII-specific immune responses and significantly increased time to progression and overall survival in those receiving vaccine therapy, as compared with published results for standard of care. Rindopepimut therefore represents a very promising therapy for patients with GBM.

Keywords::

• CDX-110
• EGFRvIII
• glioblastoma multiforme
• immunotherapy
• rindopepimut
• vaccine

Financial & competing interests disclosure

Albert Wong is a shareholder and consultant at Celldex Therapeutics and a co-inventor of the EGFRvIII sequence and EGFRvIII peptide vaccine and receives royalties to these patents. This work was supported by NIH grants CA124832 and RC2 CA148491. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.