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Front. Oncol. | doi: 10.3389/fonc.2018.00127

Immune response generated with the administration of autologous dendritic cells pulsed with an allogenic tumoral cell lines lysate in patients with newly diagnosed DIPG

Daniel Benitez-Ribas1, Raquel Cabezon1, Georgina Flórez-Grau1,  Mari Carmen Molero2, Patricia Puerta3, Antonio Guillen3, Sonia Paco4, 5, Angel M. Carcaboso4, 5, Vicente Santa-Maria4, 6,  Ofelia Cruz4, 6, Carmen De Torres4, 5, Noelia Salvador4, 5, Manel Juan1*,  Jaume Mora4 and  Andres Morales La Madrid4, 5, 6*
  • 1Department of Immunology, IDIBAPS, Hospital Clínic de Barcelona, Spain
  • 2Department of Clinical Trials, Hospital Sant Joan de Déu Barcelona, Spain
  • 3Neurosurgery, Hospital Sant Joan de Déu Barcelona, Spain
  • 4Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu Barcelona, Spain
  • 5Laboratory of Developmental Cancer, Hospital Sant Joan de Déu Barcelona, Spain
  • 6Neuro Oncology, Hospital Sant Joan de Déu Barcelona, Spain

Background and objective
Diffuse intrinsic pontine glioma (DIPG) is a lethal brainstem tumor in children. Dendritic cells (DCs) have T-cell stimulatory capacity and, therefore, potential antitumor activity for disease control. DCs vaccines have been shown to reactivate tumor-specific T cells in both clinical and pre-clinical settings. We designed a phase Ib immunotherapy (IT) clinical trial with the use of autologous dendritic cells (ADCs) pulsed with an allogeneic tumors cell-lines lysate (ATCL) in patients with newly diagnosed DIPG after irradiation (RT).

Methods
Nine patients with newly diagnosed DIPG met enrollment criteria. Autologous dendritic cell vaccines (ADCV) were prepared from monocytes obtained by leukapheresis. Five ADCV doses were administered intradermally during induction phase. In the absence of tumor progression, patients received 3 boosts of tumor lysate every three months during the maintenance phase.

Results
Vaccine fabrication was feasible in all patients included in the study. Non-specific KLH (9/9 patients) and specific (8/9 patients) antitumor response was identified by immunologic studies in peripheral blood mononuclear cells (PBMC). Immunological responses were also confirmed in the T lymphocytes isolated from the cerebrospinal fluid (CSF) of 2 patients. Vaccine administration resulted safe in all patients treated with this schema.

Conclusions
These preliminary results demonstrate that ADCV preparation is feasible, safe and generate a DIPG-specific immune response detected in PBMC and CSF. This strategy shows a promising backbone for future schemas of combination immunotherapy.

Keywords: Immunotherapy, dendritic, cell, Vaccination, dipg

Received: 16 Jan 2018; Accepted: 06 Apr 2018.

Edited by:

Peter Bader, Universitätsklinikum Frankfurt, Germany

Reviewed by:

George Jallo, Johns Hopkins University, United States
Joseph L. Lasky, Cure 4 The Kids, United States  

Copyright: © 2018 Benitez-Ribas, Cabezon, Flórez-Grau, Molero, Puerta, Guillen, Paco, Carcaboso, Santa-Maria, Cruz, De Torres, Salvador, Juan, Mora and Morales La Madrid. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
MD, PhD. Manel Juan, Hospital Clínic de Barcelona, Department of Immunology, IDIBAPS, Barcelona, Spain, mjuan@clinic.cat
MD. Andres Morales La Madrid, Hospital Sant Joan de Déu Barcelona, Department of Pediatric Hematology and Oncology, Barcelona, Spain, amorales@hsjdbcn.org