title: First clinical results of a personalized immunotherapeutic vaccine against recurrent, incompletely resected, treatment-resistant glioblastoma multiforme (GBM) tumors, based on combined allo- and auto-immune tumor reactivity.
abstract: Glioblastoma multiforme (GBM) patients have a poor prognosis. After tumor recurrence statistics suggest an imminent death within 1-4.5 months. Supportive preclinical data, from a rat model, provided the rational for a prototype clinical vaccine preparation, named Gliovac (or ERC 1671) composed of autologous antigens, derived from the patient's surgically removed tumor tissue, which is administered together with allogeneic antigens from glioma tissue resected from other GBM patients. We now report the first results of the Gliovac treatment for treatment-resistant GBM patients. Nine (9) recurrent GBM patients, after standard of care treatment, including surgery radio- and chemotherapy temozolomide, and for US patients, also bevacizumab (Avastin™), were treated under a compassionate use/hospital exemption protocol. Gliovac was given intradermally, together with human GM-CSF (Leukine(®)), and preceded by a regimen of regulatory T cell-depleting, low-dose cyclophosphamide. Gliovac administration in patients that have failed standard of care therapies showed minimal toxicity and enhanced overall survival (OS). Six-month (26 weeks) survival for the nine Gliovac patients was 100% versus 33% in control group. At week 40, the published overall survival was 10% if recurrent, reoperated patients were not treated. In the Gliovac treated group, the survival at 40 weeks was 77%. Our data suggest that Gliovac has low toxicity and a promising efficacy. A phase II trial has recently been initiated in recurrent, bevacizumab naïve GBM patients (NCT01903330).
authors: Cell Biology & Immunology Group, Wageningen University, PO Box 338, 6700 AH Wageningen, The Netherlands; Epitopoietic Research Corporation (ERC), Namur, Belgium; Epitopoietic Research Corporation (ERC), Schaijk, The Netherlands. Electronic address: Schijns.virgil@gmail.com.
authors: Virgil E J C
authors: VE
authors: Schijns
authors: Epitopoietic Research Corporation (ERC), Namur, Belgium; Epitopoietic Research Corporation (ERC), Schaijk, The Netherlands.
authors: Chrystel
authors: C
authors: Pretto
authors: Epitopoietic Research Corporation (ERC), Namur, Belgium; Epitopoietic Research Corporation (ERC), Schaijk, The Netherlands.
authors: Laurent
authors: L
authors: Devillers
authors: Epitopoietic Research Corporation (ERC), Namur, Belgium; Epitopoietic Research Corporation (ERC), Schaijk, The Netherlands.
authors: Denis
authors: D
authors: Pierre
authors: Department of Pathology, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
authors: Florence M
authors: FM
authors: Hofman
authors: Department of Neurosurgery, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA; Epitopoietic Research Corporation (ERC), 1055 E Colorado Blvd., Suite 500, Pasadena, CA 91106, USA.
authors: Thomas C
authors: TC
authors: Chen
authors: Department of Neurology, Arlon Hospital, Arlon, Belgium.
authors: Pascal
authors: P
authors: Mespouille
authors: Department of Neurosurgery, Arlon and Libramont Hospital, Arlon and Libramont, Belgium.
authors: Peter
authors: P
authors: Hantos
authors: Department of Oncology, Arlon Hospital, Arlon, Belgium.
authors: Philippe
authors: P
authors: Glorieux
authors: Department of Neurology/Neurosurgery, University of California at Irvine, UC Irvine Medical Center, Irvine, CA, USA.
authors: Daniela A
authors: DA
authors: Bota
authors: Cell Biology & Immunology Group, Wageningen University, PO Box 338, 6700 AH Wageningen, The Netherlands; Epitopoietic Research Corporation (ERC), Namur, Belgium; Epitopoietic Research Corporation (ERC), Schaijk, The Netherlands; Department of Neurosurgery, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA; Epitopoietic Research Corporation (ERC), 1055 E Colorado Blvd., Suite 500, Pasadena, CA 91106, USA; Department of Neurosurgery, Arlon and Libramont Hospital, Arlon and Libramont, Belgium; Department of Neurology/Neurosurgery, University of California at Irvine, UC Irvine Medical Center, Irvine, CA, USA. Electronic address: tstath@hotmail.com.
authors: Apostolos
authors: A
authors: Stathopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D005260:Female; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D016233:Immunotherapy, Active / Q000009:adverse effects / Q000379:methods*; D008297:Male; D000090204:Mesothelin; D008875:Middle Aged; D057285:Precision Medicine / Q000379:methods*; D051381:Rats; D012008:Recurrence; D016896:Treatment Outcome; D014481:United States; D014611:Vaccination / Q000009:adverse effects / Q000379:methods*
keywords: Allogeneic; Autologous; Glioma; Immunotherapy; Vaccine