Cargando…

Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials

Background: Malignant pleural mesothelioma (MPM) is a fatal neoplasm with, if untreated, poor survival of approximately nine months from diagnosis. Until recently, phase II–III immunotherapy trials did not show any significant benefit. The lack of immunotherapy efficacy can be explained by the fact...

Descripción completa

Detalles Bibliográficos
Autores principales: Dumoulin, Daphne W., Cornelissen, Robin, Bezemer, Koen, Baart, Sara J., Aerts, Joachim G. J. V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158710/
https://www.ncbi.nlm.nih.gov/pubmed/34069348
http://dx.doi.org/10.3390/vaccines9050525
_version_ 1783699921532092416
author Dumoulin, Daphne W.
Cornelissen, Robin
Bezemer, Koen
Baart, Sara J.
Aerts, Joachim G. J. V.
author_facet Dumoulin, Daphne W.
Cornelissen, Robin
Bezemer, Koen
Baart, Sara J.
Aerts, Joachim G. J. V.
author_sort Dumoulin, Daphne W.
collection PubMed
description Background: Malignant pleural mesothelioma (MPM) is a fatal neoplasm with, if untreated, poor survival of approximately nine months from diagnosis. Until recently, phase II–III immunotherapy trials did not show any significant benefit. The lack of immunotherapy efficacy can be explained by the fact that mesothelioma is a tumor with an “immune desert” phenotype, meaning a non-inflamed tumor characterized by low T-cell infiltration. By administration of DCs, which were ex-vivo cultured, exposed to (tumor-associated) antigens, and subsequently activated, this “immune desert” phenotype might be turned into an “inflamed” phenotype. Three phase I/II studies have been performed and published using activated DCs, which support this concept. We here report on the long-term survival of patients treated with DCs in three phase I/II studies. Methods: Survival data of the phase I/II trials using DC therapy in MPM patients were obtained and subsequently analyzed. In the first two trials, DCs were loaded with autologous tumor lysate. In the third trial, DCs were loaded with allogeneic mesothelioma tumor cell line lysate. Results: In the three studies combined, 29 patients with MPM were treated with DC vaccination between 2006 and 2015. At data cut-off, the median OS was 27 months (95% CI: 21–47 months). OS at 2 years was 55.2% (95% CI: 39.7–76.6%), and OS at 5 years was 20.7% (95% CI: 10.1–42.2%). Conclusions: The long-term survival of DC therapy in MPM in these three trials is promising, which is the basis for the randomized phase II/III DENIM study. This DENIM study is currently enrolling, and the results of which have to be awaited for definite conclusions.
format Online
Article
Text
id pubmed-8158710
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-81587102021-05-28 Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials Dumoulin, Daphne W. Cornelissen, Robin Bezemer, Koen Baart, Sara J. Aerts, Joachim G. J. V. Vaccines (Basel) Communication Background: Malignant pleural mesothelioma (MPM) is a fatal neoplasm with, if untreated, poor survival of approximately nine months from diagnosis. Until recently, phase II–III immunotherapy trials did not show any significant benefit. The lack of immunotherapy efficacy can be explained by the fact that mesothelioma is a tumor with an “immune desert” phenotype, meaning a non-inflamed tumor characterized by low T-cell infiltration. By administration of DCs, which were ex-vivo cultured, exposed to (tumor-associated) antigens, and subsequently activated, this “immune desert” phenotype might be turned into an “inflamed” phenotype. Three phase I/II studies have been performed and published using activated DCs, which support this concept. We here report on the long-term survival of patients treated with DCs in three phase I/II studies. Methods: Survival data of the phase I/II trials using DC therapy in MPM patients were obtained and subsequently analyzed. In the first two trials, DCs were loaded with autologous tumor lysate. In the third trial, DCs were loaded with allogeneic mesothelioma tumor cell line lysate. Results: In the three studies combined, 29 patients with MPM were treated with DC vaccination between 2006 and 2015. At data cut-off, the median OS was 27 months (95% CI: 21–47 months). OS at 2 years was 55.2% (95% CI: 39.7–76.6%), and OS at 5 years was 20.7% (95% CI: 10.1–42.2%). Conclusions: The long-term survival of DC therapy in MPM in these three trials is promising, which is the basis for the randomized phase II/III DENIM study. This DENIM study is currently enrolling, and the results of which have to be awaited for definite conclusions. MDPI 2021-05-19 /pmc/articles/PMC8158710/ /pubmed/34069348 http://dx.doi.org/10.3390/vaccines9050525 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Dumoulin, Daphne W.
Cornelissen, Robin
Bezemer, Koen
Baart, Sara J.
Aerts, Joachim G. J. V.
Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials
title Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials
title_full Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials
title_fullStr Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials
title_full_unstemmed Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials
title_short Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials
title_sort long-term follow-up of mesothelioma patients treated with dendritic cell therapy in three phase i/ii trials
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158710/
https://www.ncbi.nlm.nih.gov/pubmed/34069348
http://dx.doi.org/10.3390/vaccines9050525
work_keys_str_mv AT dumoulindaphnew longtermfollowupofmesotheliomapatientstreatedwithdendriticcelltherapyinthreephaseiiitrials
AT cornelissenrobin longtermfollowupofmesotheliomapatientstreatedwithdendriticcelltherapyinthreephaseiiitrials
AT bezemerkoen longtermfollowupofmesotheliomapatientstreatedwithdendriticcelltherapyinthreephaseiiitrials
AT baartsaraj longtermfollowupofmesotheliomapatientstreatedwithdendriticcelltherapyinthreephaseiiitrials
AT aertsjoachimgjv longtermfollowupofmesotheliomapatientstreatedwithdendriticcelltherapyinthreephaseiiitrials