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Autologous Dendritic Cells Pulsed with Allogeneic Tumor Cell Lysate in Mesothelioma: From Mouse to Human.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2018 Feb 15; Vol. 24 (4), pp. 766-776. Date of Electronic Publication: 2017 Dec 12. - Publication Year :
- 2018
-
Abstract
- Purpose: Mesothelioma has been regarded as a nonimmunogenic tumor, which is also shown by the low response rates to treatments targeting the PD-1/PD-L1 axis. Previously, we demonstrated that autologous tumor lysate-pulsed dendritic cell (DC) immunotherapy increased T-cell response toward malignant mesothelioma. However, the use of autologous tumor material hampers implementation in large clinical trials, which might be overcome by using allogeneic tumor cell lines as tumor antigen source. The purpose of this study was to investigate whether allogeneic lysate-pulsed DC immunotherapy is effective in mice and safe in humans. Experimental Design: First, in two murine mesothelioma models, mice were treated with autologous DCs pulsed with either autologous or allogeneic tumor lysate or injected with PBS (negative control). Survival and tumor-directed T-cell responses of these mice were monitored. Results were taken forward in a first-in-human clinical trial, in which 9 patients were treated with 10, 25, or 50 million DCs per vaccination. DC vaccination consisted of autologous monocyte-derived DCs pulsed with tumor lysate from five mesothelioma cell lines. Results: In mice, allogeneic lysate-pulsed DC immunotherapy induced tumor-specific T cells and led to an increased survival, to a similar extent as DC immunotherapy with autologous tumor lysate. In the first-in-human clinical trial, no dose-limiting toxicities were established and radiographic responses were observed. Median PFS was 8.8 months [95% confidence interval (CI), 4.1-20.3] and median OS not reached (median follow-up = 22.8 months). Conclusions: DC immunotherapy with allogeneic tumor lysate is effective in mice and safe and feasible in humans. Clin Cancer Res; 24(4); 766-76. ©2017 AACR .<br /> (©2017 American Association for Cancer Research.)
- Subjects :
- Aged
Animals
Autografts
Cancer Vaccines administration & dosage
Cell Extracts immunology
Cell Line, Tumor
Cells, Cultured
Female
Humans
Lung Neoplasms immunology
Male
Mesothelioma immunology
Mesothelioma, Malignant
Mice, Inbred BALB C
Mice, Inbred CBA
Middle Aged
Survival Analysis
Allogeneic Cells immunology
Cancer Vaccines immunology
Dendritic Cells immunology
Immunotherapy methods
Lung Neoplasms therapy
Mesothelioma therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 24
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 29233904
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-17-2522