Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Clin Oncol. Nov 10, 2012; 3(11): 142-149
Published online Nov 10, 2012. doi: 10.5306/wjco.v3.i11.142
Dendritic cell vaccination in glioblastoma after fluorescence-guided resection
Ricardo Diez Valle, Ascension Lopez-Diaz de Cerio, Susana Inoges, Sonia Tejada, Fernando Pastor, Helena Villanueva, Jaime Gallego, Jaime Espinos, Javier Aristu, Miguel Angel Idoate, Enrique Andreu, Maurizio Bendandi
Ricardo Diez Valle, Sonia Tejada, Department of Neurosurgery, University of Navarra Hospital, 31008 Pamplona, Navarra, Spain
Ascension Lopez-Diaz de Cerio, Susana Inoges, Fernando Pastor, Helena Villanueva, Maurizio Bendandi, Lab of Immunotherapy, CIMA, 31008 Pamplona, Navarra, Spain
Susana Inoges, Maurizio Bendandi, Immunotherapy Program, University of Navarra Hospital, 31008 Pamplona, Navarra, Spain
Jaime Gallego, Department of Neurology, University of Navarra Hospital, 31008 Pamplona, Navarra, Spain
Jaime Espinos, Javier Aristu, Department of Oncology, University of Navarra Hospital, 31008 Pamplona, Navarra, Spain
Miguel Angel Idoate, Department of Pathology, University of Navarra Hospital, 31008 Pamplona, Navarra, Spain
Enrique Andreu, Cell Therapy Area, University of Navarra Hospital, 31008 Pamplona, Navarra, Spain
Author contributions: All authors equally contributed to this work.
Supported by Spanish Health Ministry Grant MCI EC08/00186
Correspondence to: Maurizio Bendandi, MD, PhD, Director, Lab of Immunotherapy, CIMA, Cima Avda. Pio XII 55, 31008 Pamplona, Navarra, Spain. mbendandi@unav.es
Telephone: +34-948-255400 Fax: +34-948-296500
Received: August 22, 2012
Revised: October 22, 2012
Accepted: November 2, 2012
Published online: November 10, 2012
Processing time: 217 Days and 18.5 Hours
Abstract

AIM: To assess whether the addition of a customized, active immunotherapy to standard of care including fluorescence-guided surgery, may provide hints of an improved survival for patients with poor-prognosis, incurable glioblastoma multiform.

METHODS: Preliminary to our ongoing, phase-II clinical trial, we conducted a small pilot study enrolling five consecutive patients with resectable glioblastoma. In terms of Recursive Partitioning Analysis, four patients were class V and one was class IV. In all five cases, fluorescence-guided surgery was employed, followed by rapid steroid discontinuation. Patients were then treated with a combination of standard radio-chemotherapy with temozolomide and tumor lysate-pulsed, mature dendritic cell-based vaccinations.

RESULTS: Though all five patients ultimately progressed, with any further treatment left to the sole decision of the treating oncologist, active immunotherapy was very well tolerated and induced specific immune responses in all three patients for whom enough material was available for such an assessment. Median progression-free survival was 16.1 mo. Even more important, median and mean overall survival were 27 mo and 26 mo, respectively. Three patients have died with an overall survival of 9 mo, 27 mo and 27.4 mo, while the other two are still alive at 32 mo and 36 mo, the former receiving treatment with bevacizumab, while the latter has now been off therapy for 12 mo. Four of five patients were alive at two years.

CONCLUSION: Active immunotherapy with tumor lysate-pulsed, autologous dendritic cells is feasible, safe, well tolerated and biologically efficacious. A phase-II study is ongoing to possibly improve further on our very encouraging clinical results.

Keywords: Immunotherapy; Glioblastoma; Fluorescence-guided surgery; Dendritic cells; Tumor-lysate