Targeting EGF receptor variant III: tumor-specific peptide vaccination for malignant gliomas.
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.
Stanford University, 1201 Welch Road, MSLS P105, Stanford, CA 94305, USA.
Catherine A
CA
Del Vecchio
Gordon
G
Li
Albert J
AJ
Wong
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000276:immunology*; D005909:Glioblastoma / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D041681:NIH 3T3 Cells; D016896:Treatment Outcome; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use
D019496:Cancer Vaccines; D022223:Vaccines, Subunit; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors; C558237:rindopepimut