Epidermal growth factor receptor and variant III targeted immunotherapy

Abstract

Immunotherapeutic approaches to cancer have shown remarkable promise. A critical barrier to successfully executing such immune-mediated interventions is the selection of safe yet immunogenic targets. As patient deaths have occurred when tumor-associated antigens shared by normal tissue have been targeted by strong cellular immunotherapeutic platforms, route of delivery, target selection and the immune-mediated approach undertaken must work together to maximize efficacy with safety. Selected tumor-specific targets can spare potential toxicity to normal tissue; however, they are far less common than tumor-associated antigens and may not be present on all patients. In the context of immunotherapy for high-grade glioma, 2 of the most prominently studied antigens are the tumor-associated epidermal growth factor receptor and its tumor-specific genetic deletion variant III. In this review, we will summarize the immune-mediated strategies employed against these targets as well as the caveats particular to these approaches.

Effects of combined radiosurgery and temozolomide therapy on epidermal growth factor receptor and variant III in glioblastoma multiforme

“…Previous studies have indicated that a high expression level of EGFRvIII is positively correlated with the invasion abilities of GBM cells. Previous studies have also indicated that 30–60% of GBM patients exhibit high expression levels of EGFRvIII, and these mutations are not detected in normal brain tissues of adult humans or other normal tissues ( 17 – 19 ). Therefore, EGFRvIII is a good target for GBM gene therapy.…”

Immunotherapy in Glioblastoma: Current Shortcomings and Future Perspectives

“…In gliomas, the variant III of the epidermal growth factor receptor (EGFRvIII), which results from an in-frame intragenic deletion of EGFR exons 2-7, is present in approximately 20% to 30% of glioblastomas and a recognized target in many peptide vaccination studies [21][22][23]. A peptide vaccine targeting EGFRvIII (rindopepimut) displayed evidence for immunogenicity and efficacy in early phase trials for EGFRvIII+ glioblastoma patients [24][25][26][27].…”

Concepts for Immunotherapies in Gliomas

“…EGFRvIII is detected in approximately 20% to 30% of glioblastoma samples, and in general is coexpressed with the wild-type variant on a single-cell level. 42 A peptide vaccine conjugated to the adjuvant keyhole limpet hemocyanin (KLH) induces robust anti-EGFRvIII antibody responses in patients with EGFRvIII-positive tumors. 43 After encouraging results from noncontrolled phase I/II studies, the randomized ACT-IV registration trial, tested the efficacy of EGFRvIII Pep-KLH (rindopepimut) compared with placebo when combined with temozolomide radiochemotherapy in patients with newly diagnosed EGFRvIII-positive glioblastoma (NCT01480479).…”