Prospect of rindopepimut in the treatment of glioblastoma. (3rd April 2017)

• Record Type: Journal Article
• Authors: Elsamadicy, Aladine A.; Chongsathidkiet, Pakawat; Desai, Rupen; Woroniecka, Karolina; Farber, S. Harrison; Fecci, Peter E.; Sampson, John H.
• Is Part Of: Expert opinion on biological therapy. Volume 17:Number 4(2017:Apr.)
• Page Start: 507
• Page End: 513
• Publication Date: 2017-04-03
• Subjects: Glioblastoma -- immunotherapy -- clinical trials -- rindopepimut -- peptide vaccine -- EGFRvIII; Gene therapy -- Periodicals; Protein drugs -- Periodicals; Peptide drugs -- Periodicals; Immunotherapy -- Periodicals; Drug delivery systems -- Periodicals; 615.5
• DOI: 10.1080/14712598.2017.1299705
• Languages: English
• ISSNs: 1471-2598

Abstract

ABSTRACT: Introduction : Rindopepimut (CDX-110) is a peptide vaccine that targets epidermal growth factor receptor variant III (EGFRvIII), a tumor-specific epitope expressed in the most common and lethal primary malignant neoplasm of the brain – glioblastoma (GBM). Areas covered : The EGFRvIII mutation introduces an 801 base pair in-frame deletion of the extracellular domain of the transmembrane tyrosine kinase, resulting in constitutive kinase activity, amplification of cell growth, and inhibition of apoptosis. Rindopepimut contains a 14mer amino acid peptide spanning the EGFRvIII mutation site that is conjugated to keyhole limpet hemocyanin (KLH). The EGFRvIII neoantigen is exclusively present on GBM cells, providing rindopepimut tumor-specific activity. The authors review rindopepimut's clinical efficacy, administration, safety, and prospects in the treatment of GBM. Expert opinion : Rindopepimut showed clinical benefit and significant efficacy in phase II clinical trials, including as part of a multi-immunotherapy approach. A phase III clinical trial was terminated early, however, as it was deemed likely the study would fail to meet its primary endpoint. Longer term and sub-group analyses will be necessary to better understand rindopepimut's future role in GBM therapy.