A pilot study of an autologous tumor-derived autophagosome vaccine with docetaxel in patients with stage IV non-small cell lung cancer
Abstract Background Tumor-derived autophagosome vaccines (DRibbles) have the potential to broaden immune response to poorly immunogenic tumors. Methods Autologous vaccine generated from tumor cells harvested from pleural effusions was administered to patients with advanced NSCLC with the objectives...
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doaj-51a617bc9e0947b2b40212ed699e06aa2020-11-25T02:05:11ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262017-12-015111410.1186/s40425-017-0306-6A pilot study of an autologous tumor-derived autophagosome vaccine with docetaxel in patients with stage IV non-small cell lung cancerRachel E. Sanborn0Helen J. Ross1Sandra Aung2Anupama Acheson3Tarsem Moudgil4Sachin Puri5Traci Hilton6Brenda Fisher7Todd Coffey8Christopher Paustian9Michael Neuberger10Edwin Walker11Hong-Ming Hu12Walter J. Urba13Bernard A. Fox14Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical CenterMayo Clinic ArizonaUbiVacRobert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical CenterLaboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer CenterLaboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer CenterUbiVacRobert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical CenterRobert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical CenterLaboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer CenterLaboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer CenterImmunological Monitoring Laboratory, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer CenterUbiVacRobert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical CenterUbiVacAbstract Background Tumor-derived autophagosome vaccines (DRibbles) have the potential to broaden immune response to poorly immunogenic tumors. Methods Autologous vaccine generated from tumor cells harvested from pleural effusions was administered to patients with advanced NSCLC with the objectives of assessing safety and immune response. Four patients were vaccinated and evaluable for immune response; each received two to four doses of vaccine. Study therapy included two cycles of docetaxel 75 mg/m2 on days 1 and 29 to treat the tumor, release hidden antigens and produce lymphopenia. DRibbles were to be administered intradermally on days 14, 43, 57, 71, and 85, together with GM-CSF (50 μg/d x 6d, administered via SQ mini pump). Peripheral blood was tested for immune parameters at baseline and at each vaccination. Results Three of four patients had tumor cells available for testing. Autologous tumor-specific immune response was seen in two of the three, manifested by IL-5 (1 patient after 3 doses), and IFN-γ, TNF-α, IL-5, IL-10 (after 4 doses in one patient). All 4 patients had evidence of specific antibody responses against potential tumor antigens. All patients came off study after 4 or fewer vaccine treatments due to progression of disease. No significant immune toxicities were seen during the course of the study. Conclusions DRibble vaccine given with GM-CSF appeared safe and capable of inducing an immune response against tumor cells in this small, pilot study. There was no evidence of efficacy in this small poor-prognosis patient population, with treatment not feasible. Trial registration NCT00850785, initial registration date February 23, 2009.http://link.springer.com/article/10.1186/s40425-017-0306-6Non-small cell lung cancerVaccinePleural effusionImmunotherapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rachel E. Sanborn Helen J. Ross Sandra Aung Anupama Acheson Tarsem Moudgil Sachin Puri Traci Hilton Brenda Fisher Todd Coffey Christopher Paustian Michael Neuberger Edwin Walker Hong-Ming Hu Walter J. Urba Bernard A. Fox |
spellingShingle |
Rachel E. Sanborn Helen J. Ross Sandra Aung Anupama Acheson Tarsem Moudgil Sachin Puri Traci Hilton Brenda Fisher Todd Coffey Christopher Paustian Michael Neuberger Edwin Walker Hong-Ming Hu Walter J. Urba Bernard A. Fox A pilot study of an autologous tumor-derived autophagosome vaccine with docetaxel in patients with stage IV non-small cell lung cancer Journal for ImmunoTherapy of Cancer Non-small cell lung cancer Vaccine Pleural effusion Immunotherapy |
author_facet |
Rachel E. Sanborn Helen J. Ross Sandra Aung Anupama Acheson Tarsem Moudgil Sachin Puri Traci Hilton Brenda Fisher Todd Coffey Christopher Paustian Michael Neuberger Edwin Walker Hong-Ming Hu Walter J. Urba Bernard A. Fox |
author_sort |
Rachel E. Sanborn |
title |
A pilot study of an autologous tumor-derived autophagosome vaccine with docetaxel in patients with stage IV non-small cell lung cancer |
title_short |
A pilot study of an autologous tumor-derived autophagosome vaccine with docetaxel in patients with stage IV non-small cell lung cancer |
title_full |
A pilot study of an autologous tumor-derived autophagosome vaccine with docetaxel in patients with stage IV non-small cell lung cancer |
title_fullStr |
A pilot study of an autologous tumor-derived autophagosome vaccine with docetaxel in patients with stage IV non-small cell lung cancer |
title_full_unstemmed |
A pilot study of an autologous tumor-derived autophagosome vaccine with docetaxel in patients with stage IV non-small cell lung cancer |
title_sort |
pilot study of an autologous tumor-derived autophagosome vaccine with docetaxel in patients with stage iv non-small cell lung cancer |
publisher |
BMJ Publishing Group |
series |
Journal for ImmunoTherapy of Cancer |
issn |
2051-1426 |
publishDate |
2017-12-01 |
description |
Abstract Background Tumor-derived autophagosome vaccines (DRibbles) have the potential to broaden immune response to poorly immunogenic tumors. Methods Autologous vaccine generated from tumor cells harvested from pleural effusions was administered to patients with advanced NSCLC with the objectives of assessing safety and immune response. Four patients were vaccinated and evaluable for immune response; each received two to four doses of vaccine. Study therapy included two cycles of docetaxel 75 mg/m2 on days 1 and 29 to treat the tumor, release hidden antigens and produce lymphopenia. DRibbles were to be administered intradermally on days 14, 43, 57, 71, and 85, together with GM-CSF (50 μg/d x 6d, administered via SQ mini pump). Peripheral blood was tested for immune parameters at baseline and at each vaccination. Results Three of four patients had tumor cells available for testing. Autologous tumor-specific immune response was seen in two of the three, manifested by IL-5 (1 patient after 3 doses), and IFN-γ, TNF-α, IL-5, IL-10 (after 4 doses in one patient). All 4 patients had evidence of specific antibody responses against potential tumor antigens. All patients came off study after 4 or fewer vaccine treatments due to progression of disease. No significant immune toxicities were seen during the course of the study. Conclusions DRibble vaccine given with GM-CSF appeared safe and capable of inducing an immune response against tumor cells in this small, pilot study. There was no evidence of efficacy in this small poor-prognosis patient population, with treatment not feasible. Trial registration NCT00850785, initial registration date February 23, 2009. |
topic |
Non-small cell lung cancer Vaccine Pleural effusion Immunotherapy |
url |
http://link.springer.com/article/10.1186/s40425-017-0306-6 |
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