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

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 bot...

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Autores: Benítez-Ribas, Daniel, Cabezón Cabello, Raquel, Flórez Grau, Georgina, Molero, Mari Carmen, Puerta, Patricia, Guillen, Antonio, González Navarro, E. Azucena, Paco Mercader, Sonia, Carcaboso, Ángel M., Santa-Maria Lopez, Vicente, Cruz Martínez, Ofelia, Torres Gómez-Pallete, Carmen de, Salvador, Noelia, Juan, Manel, Mora Graupera, Jaume, Morales La Madrid, Andrés
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/139674
Acceso en línea:https://hdl.handle.net/2445/139674
Access Level:acceso abierto
Palabra clave:Immunoteràpia
Tumors
Vacunació
Cèl·lules dendrítiques
Immunotheraphy
Vaccination
Dendritic cells
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spelling Immune response generated with the administration of autologous dendritic cells pulsed with an allogenic tumoral cell lines lysate in patients with newly diagnosed DIPGBenítez-Ribas, DanielCabezón Cabello, RaquelFlórez Grau, GeorginaMolero, Mari CarmenPuerta, PatriciaGuillen, AntonioGonzález Navarro, E. AzucenaPaco Mercader, SoniaCarcaboso, Ángel M.Santa-Maria Lopez, VicenteCruz Martínez, OfeliaTorres Gómez-Pallete, Carmen deSalvador, NoeliaJuan, ManelMora Graupera, JaumeMorales La Madrid, AndrésImmunoteràpiaTumorsVacunacióCèl·lules dendrítiquesImmunotheraphyTumorsVaccinationDendritic cellsBackground 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.Frontiers Media2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/139674Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fonc.2018.00127Frontiers in Oncology, 2018, vol. 8, p. 127https://doi.org/10.3389/fonc.2018.00127cc-by (c) Benítez-Ribas, Daniel et al., 2018http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1396742026-05-27T06:46:51Z
dc.title.none.fl_str_mv Immune response generated with the administration of autologous dendritic cells pulsed with an allogenic tumoral cell lines lysate in patients with newly diagnosed DIPG
title Immune response generated with the administration of autologous dendritic cells pulsed with an allogenic tumoral cell lines lysate in patients with newly diagnosed DIPG
spellingShingle Immune response generated with the administration of autologous dendritic cells pulsed with an allogenic tumoral cell lines lysate in patients with newly diagnosed DIPG
Benítez-Ribas, Daniel
Immunoteràpia
Tumors
Vacunació
Cèl·lules dendrítiques
Immunotheraphy
Tumors
Vaccination
Dendritic cells
title_short Immune response generated with the administration of autologous dendritic cells pulsed with an allogenic tumoral cell lines lysate in patients with newly diagnosed DIPG
title_full Immune response generated with the administration of autologous dendritic cells pulsed with an allogenic tumoral cell lines lysate in patients with newly diagnosed DIPG
title_fullStr Immune response generated with the administration of autologous dendritic cells pulsed with an allogenic tumoral cell lines lysate in patients with newly diagnosed DIPG
title_full_unstemmed Immune response generated with the administration of autologous dendritic cells pulsed with an allogenic tumoral cell lines lysate in patients with newly diagnosed DIPG
title_sort Immune response generated with the administration of autologous dendritic cells pulsed with an allogenic tumoral cell lines lysate in patients with newly diagnosed DIPG
dc.creator.none.fl_str_mv Benítez-Ribas, Daniel
Cabezón Cabello, Raquel
Flórez Grau, Georgina
Molero, Mari Carmen
Puerta, Patricia
Guillen, Antonio
González Navarro, E. Azucena
Paco Mercader, Sonia
Carcaboso, Ángel M.
Santa-Maria Lopez, Vicente
Cruz Martínez, Ofelia
Torres Gómez-Pallete, Carmen de
Salvador, Noelia
Juan, Manel
Mora Graupera, Jaume
Morales La Madrid, Andrés
author Benítez-Ribas, Daniel
author_facet Benítez-Ribas, Daniel
Cabezón Cabello, Raquel
Flórez Grau, Georgina
Molero, Mari Carmen
Puerta, Patricia
Guillen, Antonio
González Navarro, E. Azucena
Paco Mercader, Sonia
Carcaboso, Ángel M.
Santa-Maria Lopez, Vicente
Cruz Martínez, Ofelia
Torres Gómez-Pallete, Carmen de
Salvador, Noelia
Juan, Manel
Mora Graupera, Jaume
Morales La Madrid, Andrés
author_role author
author2 Cabezón Cabello, Raquel
Flórez Grau, Georgina
Molero, Mari Carmen
Puerta, Patricia
Guillen, Antonio
González Navarro, E. Azucena
Paco Mercader, Sonia
Carcaboso, Ángel M.
Santa-Maria Lopez, Vicente
Cruz Martínez, Ofelia
Torres Gómez-Pallete, Carmen de
Salvador, Noelia
Juan, Manel
Mora Graupera, Jaume
Morales La Madrid, Andrés
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Immunoteràpia
Tumors
Vacunació
Cèl·lules dendrítiques
Immunotheraphy
Tumors
Vaccination
Dendritic cells
topic Immunoteràpia
Tumors
Vacunació
Cèl·lules dendrítiques
Immunotheraphy
Tumors
Vaccination
Dendritic cells
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/139674
url https://hdl.handle.net/2445/139674
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fonc.2018.00127
Frontiers in Oncology, 2018, vol. 8, p. 127
https://doi.org/10.3389/fonc.2018.00127
dc.rights.none.fl_str_mv cc-by (c) Benítez-Ribas, Daniel et al., 2018
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Benítez-Ribas, Daniel et al., 2018
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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