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...

ver descrição completa

Detalhes bibliográficos
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 documento: artigo
Estado:Versão publicada
Data de publicação:2018
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/139674
Acesso em linha:https://hdl.handle.net/2445/139674
Access Level:Acceso aberto
Palavra-chave:Immunoteràpia
Tumors
Vacunació
Cèl·lules dendrítiques
Immunotheraphy
Vaccination
Dendritic cells
Descrição
Resumo: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.