The PEPvIII-KLH (CDX-110) vaccine in glioblastoma multiforme patients.
Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, resulting in non-specific toxicity. Immune targeting of tumor-specific mutations may allow for more precise eradication of neoplastic cells. EGFR variant III (EGFRvIII) is a tumor-specific mutation that is widely expressed in GBM and other neoplasms and its expression enhances tumorigenicity. This in-frame deletion mutation splits a codon, resulting in a novel glycine at the fusion junction producing a tumor-specific epitope target for cellular or humoral immunotherapy. We have previously shown that vaccination with a peptide that spans the EGFRvIII fusion junction (PEPvIII-KLH/CDX-110) is an efficacious immunotherapy in syngeneic murine models. In this review, we summarize our results in GBM patients targeting this mutation in multiple, multi-institutional Phase II immunotherapy trials. These trials demonstrated that a selected population of GBM patients who received vaccines targeting EGFRvIII had an unexpectedly long survival time. Further therapeutic strategies and potential pitfalls of using this approach are discussed.
Heimberger
Amy B
AB
University of Texas MD Anderson Cancer Center, Department of Neurosurgery, Unit 422, Houston, TX 77230-1402, USA. aheimber@mdanderson.org
Sampson
John H
JH
D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002490:Central Nervous System / Q000276:immunology; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism; D005909:Glioblastoma / Q000628:therapy*; D006433:Hemocyanins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D009154:Mutation; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011379:Prognosis
D019496:Cancer Vaccines; C520006:Pep-3 peptide; D010455:Peptides; D006433:Hemocyanins; D066246:ErbB Receptors; C032808:keyhole-limpet hemocyanin